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PloS one2015; 10(8); e0136103; doi: 10.1371/journal.pone.0136103

Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.

Abstract: Recurrent airway obstruction (RAO) is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs). We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two half-sib families and one group of unrelated horses. PBMCs were stimulated with hay dust extract, lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The total dataset consisted of 561 individual samples. We detected significant differences in the expression profiles between RAO and control horses. Differential expression (DE) was most marked upon stimulation with hay dust extract. An important novel finding was a strong upregulation of CXCL13 together with many genes involved in cell cycle regulation in stimulated samples from RAO affected horses, in addition to changes in the expression of several HIF-1 transcription factor target genes. The RAO condition alters systemic changes observed as differential expression profiles of PBMCs. Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation. Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.
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Publication Date: 2015-08-20 PubMed ID: 26292153PubMed Central: PMC4546272DOI: 10.1371/journal.pone.0136103Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates how genes and pathways involved in a common lower airway disease in horses known as Recurrent Airway Obstruction (RAO), similar to human asthma, are affected. The study found significant differences in the expression profiles between RAO-affected horses and healthy ones predominantly upon exposure to hay dust extract. A notable discovery was the strong upregulation of CXCL13 and numerous genes involved in regulating the cell cycle in stimulated samples. Changes were also seen in the HIF-1 transcription factor target genes expression.

Investigation Methodology

  • The researchers performed an RNA-sequencing on peripheral blood mononuclear cells (PBMCs) of 40 RAO affected and 45 control horses from three cohorts of Warmblood horses.
  • These PBMCs were stimulated using several irritants, prominently hay dust extract.
  • Other stimulants included lipopolysaccharides and a recombinant parasite antigen.
  • The study maintained unstimulated samples for control comparison.
  • The total dataset for the study was made up of 561 individual samples.

Discovery of Differential Expression (DE)

  • Significant differences were noted in the expression profiles between RAO affected horses and the control ones upon stimulation with hay dust extract.
  • Key findings were the strong upregulation of CXCL13 and many cell cycle regulation genes in samples from RAO affected horses.
  • The expression of several HIF-1 transcription factor target genes in the RAO affected horses also saw changes.

Impact of RAO

  • The presence of RAO condition triggered systemic changes, mainly noticeable as differential expression profiles within the PBMCs of affected horses.
  • The changes also depended on the cohort and the stimulation of samples, dominated by genes involved in immune cell development, trafficking, and cell cycle regulation.

Significance of CXCL13 and CDC20

  • Upregulated gene CXCL13 and the cell cycle regulator CDC20 play an essential role in the immune response observed in RAO personally.
  • The prominence of CXCL13 is likely linked with its derivation from macrophages or Th17.

Cite This Article

APA
Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. (2015). Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma. PLoS One, 10(8), e0136103. https://doi.org/10.1371/journal.pone.0136103

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 10
Issue: 8
Pages: e0136103
PII: e0136103

Researcher Affiliations

Pacholewska, Alicja
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Jagannathan, Vidhya
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Drögemüller, Michaela
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Klukowska-Rötzler, Jolanta
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Bern University Hospital, Bern, Switzerland.
Lanz, Simone
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.
Hamza, Eman
  • Clinical Immunology Group, Department of Clinical Research and Veterinary Public Health, University of Bern, Bern, Switzerland; Department of Zoonoses, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.
Dermitzakis, Emmanouil T
  • Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Swiss Institute of Bioinformatics, Geneva, Switzerland.
Marti, Eliane
  • Clinical Immunology Group, Department of Clinical Research and Veterinary Public Health, University of Bern, Bern, Switzerland.
Leeb, Tosso
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Gerber, Vincent
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.

MeSH Terms

  • Animals
  • Asthma / physiopathology
  • Asthma / veterinary
  • Case-Control Studies
  • Cell Cycle / physiology
  • Chemokine CXCL13 / metabolism
  • Female
  • Gene Expression Profiling / veterinary
  • Horse Diseases / physiopathology
  • Horses
  • Leukocytes, Mononuclear / physiology
  • Male
  • Models, Biological
  • Transcriptome

Conflict of Interest Statement

The authors have declared that no competing interests exist.

References

This article includes 120 references
  1. Ansotegui I, Arruda LKP, Badellino HA, Baena-Cagnani CE, Bahna SL, Baldacci S. White Book on Allergy: Update 2013. .
  2. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches.. Nat Med 2012 May 4;18(5):716-25.
    doi: 10.1038/nm.2678pubmed: 22561835google scholar: lookup
  3. Duffy DL, Martin NG, Battistutta D, Hopper JL, Mathews JD. Genetics of asthma and hay fever in Australian twins.. Am Rev Respir Dis 1990 Dec;142(6 Pt 1):1351-8.
    doi: 10.1164/ajrccm/142.6_Pt_1.1351pubmed: 2252253google scholar: lookup
  4. Edfors-Lubs ML. Allergy in 7000 twin pairs.. Acta Allergol 1971 Aug;26(4):249-85.
    doi: 10.1111/j.1398-9995.1971.tb01300.xpubmed: 4255830google scholar: lookup
  5. Strina A, Barreto ML, Cooper PJ, Rodrigues LC. Risk factors for non-atopic asthma/wheeze in children and adolescents: a systematic review.. Emerg Themes Epidemiol 2014;11:5.
    doi: 10.1186/1742-7622-11-5pmc: PMC4068161pubmed: 24963333google scholar: lookup
  6. Temesi G, Virág V, Hadadi E, Ungvári I, Fodor LE, Bikov A, Nagy A, Gálffy G, Tamási L, Horváth I, Kiss A, Hullám G, Gézsi A, Sárközy P, Antal P, Buzás E, Szalai C. Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations.. Allergy Asthma Immunol Res 2014 Nov;6(6):496-503.
    doi: 10.4168/aair.2014.6.6.496pmc: PMC4214969pubmed: 25374748google scholar: lookup
  7. Nials AT, Uddin S. Mouse models of allergic asthma: acute and chronic allergen challenge.. Dis Model Mech 2008 Nov-Dec;1(4-5):213-20.
    doi: 10.1242/dmm.000323pmc: PMC2590830pubmed: 19093027google scholar: lookup
  8. Mullane K, Williams M. Animal models of asthma: reprise or reboot?. Biochem Pharmacol 2014 Jan 1;87(1):131-9.
    doi: 10.1016/j.bcp.2013.06.026pubmed: 23831953google scholar: lookup
  9. Moran G, Folch H. Recurrent airway obstruction in horses—An allergic inflammation: A review. Vet Med (Praha) 2011;56: 1–13.
  10. Bründler P, Frey CF, Gottstein B, Nussbaumer P, Neuhaus S, Gerber V. Lower shedding of strongylid eggs by Warmblood horses with recurrent airway obstruction compared to unrelated healthy horses.. Vet J 2011 Nov;190(2):e12-e15.
    doi: 10.1016/j.tvjl.2010.12.029pubmed: 21315626google scholar: lookup
  11. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011 Oct;16(7):1027-46.
    doi: 10.1111/j.1440-1843.2011.02033.xpubmed: 21824219google scholar: lookup
  12. OBEL NJ, SCHMITERLOW CG. The action of histamine and other drugs on the bronchial tone in horses suffering from alveolar emphysema (heaves).. Acta Pharmacol Toxicol (Copenh) 1948;4(1):71-80.
    doi: 10.1111/j.1600-0773.1948.tb03489.xpubmed: 18859474google scholar: lookup
  13. Neuhaus S, Bruendler P, Frey CF, Gottstein B, Doherr MG, Gerber V. Increased parasite resistance and recurrent airway obstruction in horses of a high-prevalence family.. J Vet Intern Med 2010 Mar-Apr;24(2):407-13.
    doi: 10.1111/j.1939-1676.2009.0465.xpubmed: 20102498google scholar: lookup
  14. Swinburne JE, Bogle H, Klukowska-Rötzler J, Drögemüller M, Leeb T, Temperton E, Dolf G, Gerber V. A whole-genome scan for recurrent airway obstruction in Warmblood sport horses indicates two positional candidate regions.. Mamm Genome 2009 Aug;20(8):504-15.
    doi: 10.1007/s00335-009-9214-5pubmed: 19760324google scholar: lookup
  15. Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA. Neutrophilic airway inflammation in horses with heaves is characterized by a Th2-type cytokine profile.. Am J Respir Crit Care Med 2001 Oct 15;164(8 Pt 1):1410-3.
    doi: 10.1164/rccm2012091pubmed: 11704587google scholar: lookup
  16. Marti E, Gerber H, Essich G, Oulehla J, Lazary S. The genetic basis of equine allergic diseases. 1. Chronic hypersensitivity bronchitis.. Equine Vet J 1991 Nov;23(6):457-60.
    doi: 10.1111/j.2042-3306.1991.tb03761.xpubmed: 1778165google scholar: lookup
  17. Gerber V, Baleri D, Klukowska-Rötzler J, Swinburne JE, Dolf G. Mixed inheritance of equine recurrent airway obstruction.. J Vet Intern Med 2009 May-Jun;23(3):626-30.
    doi: 10.1111/j.1939-1676.2009.0292.xpubmed: 19645845google scholar: lookup
  18. Lanz S, Gerber V, Marti E, Rettmer H, Klukowska-Rötzler J, Gottstein B, Matthews JB, Pirie S, Hamza E. Effect of hay dust extract and cyathostomin antigen stimulation on cytokine expression by PBMC in horses with recurrent airway obstruction.. Vet Immunol Immunopathol 2013 Oct 1;155(4):229-37.
    doi: 10.1016/j.vetimm.2013.07.005pubmed: 23972861google scholar: lookup
  19. Debrue M, Hamilton E, Joubert P, Lajoie-Kadoch S, Lavoie JP. Chronic exacerbation of equine heaves is associated with an increased expression of interleukin-17 mRNA in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2005 May 1;105(1-2):25-31.
    doi: 10.1016/j.vetimm.2004.12.013pubmed: 15797472google scholar: lookup
  20. Klukowska-Rötzler J, Swinburne JE, Drögemüller C, Dolf G, Janda J, Leeb T, Gerber V. The interleukin 4 receptor gene and its role in recurrent airway obstruction in Swiss Warmblood horses.. Anim Genet 2012 Aug;43(4):450-3.
    doi: 10.1111/j.1365-2052.2011.02277.xpubmed: 22497430google scholar: lookup
  21. Horohov DW, Beadle RE, Mouch S, Pourciau SS. Temporal regulation of cytokine mRNA expression in equine recurrent airway obstruction.. Vet Immunol Immunopathol 2005 Oct 18;108(1-2):237-45.
    doi: 10.1016/j.vetimm.2005.07.013pubmed: 16098607google scholar: lookup
  22. Cordeau ME, Joubert P, Dewachi O, Hamid Q, Lavoie JP. IL-4, IL-5 and IFN-gamma mRNA expression in pulmonary lymphocytes in equine heaves.. Vet Immunol Immunopathol 2004 Jan;97(1-2):87-96.
    doi: 10.1016/j.vetimm.2003.08.013pubmed: 14700540google scholar: lookup
  23. Kleiber C, McGorum BC, Horohov DW, Pirie RS, Zurbriggen A, Straub R. Cytokine profiles of peripheral blood and airway CD4 and CD8 T lymphocytes in horses with recurrent airway obstruction.. Vet Immunol Immunopathol 2005 Mar 10;104(1-2):91-7.
    doi: 10.1016/j.vetimm.2004.10.002pubmed: 15661334google scholar: lookup
  24. Jost U, Klukowska-Rötzler J, Dolf G, Swinburne JE, Ramseyer A, Bugno M, Burger D, Blott S, Gerber V. A region on equine chromosome 13 is linked to recurrent airway obstruction in horses.. Equine Vet J 2007 May;39(3):236-41.
    doi: 10.2746/042516407X171110pubmed: 17520975google scholar: lookup
  25. Pirie RS, Dixon PM, McGorum BC. Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 3: Effect of fractionation of HDS.. Equine Vet J 2002 Jul;34(4):343-7.
    doi: 10.2746/042516402776249092pubmed: 12117105google scholar: lookup
  26. Pirie RS, Collie DD, Dixon PM, McGorum BC. Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma).. Clin Exp Allergy 2003 May;33(5):676-83.
    doi: 10.1046/j.1365-2222.2003.01640.xpubmed: 12752598google scholar: lookup
  27. Pirie RS, Dixon PM, McGorum BC. Endotoxin contamination contributes to the pulmonary inflammatory and functional response to Aspergillus fumigatus extract inhalation in heaves horses.. Clin Exp Allergy 2003 Sep;33(9):1289-96.
    doi: 10.1046/j.1365-2745.2003.01679.xpubmed: 12956737google scholar: lookup
  28. Pacholewska A, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Gerber V, Leeb T, Jagannathan V. The transcriptome of equine peripheral blood mononuclear cells.. PLoS One 2015;10(3):e0122011.
    doi: 10.1371/journal.pone.0122011pmc: PMC4366165pubmed: 25790166google scholar: lookup
  29. Boldman KG, Kriese LA, VanVleck LD, Kachman SD. A Manual for Use of MTDFREML. Washington, DC.: U. S. Department of Agriculture, Agricultural Research Service; 1993.
  30. Kehrli D, Jandova V, Fey K, Jahn P, Gerber V. Multiple hypersensitivities including recurrent airway obstruction, insect bite hypersensitivity, and urticaria in 2 warmblood horse populations.. J Vet Intern Med 2015 Jan;29(1):320-6.
    doi: 10.1111/jvim.12473pmc: PMC4858110pubmed: 25270534google scholar: lookup
  31. Ramseyer A, Gaillard C, Burger D, Straub R, Jost U, Boog C, Marti E, Gerber V. Effects of genetic and environmental factors on chronic lower airway disease in horses.. J Vet Intern Med 2007 Jan-Feb;21(1):149-56.
    pubmed: 17338163doi: 10.1892/0891-6640(2007)21[149:eogaef]2.0.co;2google scholar: lookup
  32. Laumen E, Doherr MG, Gerber V. Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families.. Equine Vet J 2010 Mar;42(2):142-8.
    doi: 10.2746/042516409X479586pubmed: 20156250google scholar: lookup
  33. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blöcker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, MacLeod JN, Penedo MC, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guérin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Røed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Lander ES, Lindblad-Toh K. Genome sequence, comparative analysis, and population genetics of the domestic horse.. Science 2009 Nov 6;326(5954):865-7.
    doi: 10.1126/science.1178158pmc: PMC3785132pubmed: 19892987google scholar: lookup
  34. Anders S, Pyl PT, Huber W. HTSeq--a Python framework to work with high-throughput sequencing data.. Bioinformatics 2015 Jan 15;31(2):166-9.
    doi: 10.1093/bioinformatics/btu638pmc: PMC4287950pubmed: 25260700google scholar: lookup
  35. Anders S, Huber W. Differential expression analysis for sequence count data.. Genome Biol 2010;11(10):R106.
    doi: 10.1186/gb-2010-11-10-r106pmc: PMC3218662pubmed: 20979621google scholar: lookup
  36. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.. Bioinformatics 2010 Jan 1;26(1):139-40.
    doi: 10.1093/bioinformatics/btp616pmc: PMC2796818pubmed: 19910308google scholar: lookup
  37. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.. Nat Genet 2000 May;25(1):25-9.
    doi: 10.1038/75556.Genepmc: PMC3037419pubmed: 10802651google scholar: lookup
  38. Nogales-Cadenas R, Carmona-Saez P, Vazquez M, Vicente C, Yang X, Tirado F, Carazo JM, Pascual-Montano A. GeneCodis: interpreting gene lists through enrichment analysis and integration of diverse biological information.. Nucleic Acids Res 2009 Jul;37(Web Server issue):W317-22.
    doi: 10.1093/nar/gkp416pmc: PMC2703901pubmed: 19465387google scholar: lookup
  39. Carmona-Saez P, Chagoyen M, Tirado F, Carazo JM, Pascual-Montano A. GENECODIS: a web-based tool for finding significant concurrent annotations in gene lists.. Genome Biol 2007;8(1):R3.
    doi: 10.1186/gb-2007-8-1-r3pmc: PMC1839127pubmed: 17204154google scholar: lookup
  40. Tabas-Madrid D, Nogales-Cadenas R, Pascual-Montano A. GeneCodis3: a non-redundant and modular enrichment analysis tool for functional genomics.. Nucleic Acids Res 2012 Jul;40(Web Server issue):W478-83.
    doi: 10.1093/nar/gks402pmc: PMC3394297pubmed: 22573175google scholar: lookup
  41. Kinsella RJ, Kähäri A, Haider S, Zamora J, Proctor G, Spudich G, Almeida-King J, Staines D, Derwent P, Kerhornou A, Kersey P, Flicek P. Ensembl BioMarts: a hub for data retrieval across taxonomic space.. Database (Oxford) 2011;2011:bar030.
    doi: 10.1093/database/bar030pmc: PMC3170168pubmed: 21785142google scholar: lookup
  42. Pu D, Wang W. Toll-like receptor 4 agonist, lipopolysaccharide, increases the expression levels of cytokines and chemokines in human peripheral blood mononuclear cells.. Exp Ther Med 2014 Dec;8(6):1914-1918.
    doi: 10.3892/etm.2014.2025pmc: PMC4218705pubmed: 25371755google scholar: lookup
  43. Karnati HK, Pasupuleti SR, Kandi R, Undi RB, Sahu I, Kannaki TR, Subbiah M, Gutti RK. TLR-4 signalling pathway: MyD88 independent pathway up-regulation in chicken breeds upon LPS treatment.. Vet Res Commun 2015 Mar;39(1):73-8.
    doi: 10.1007/s11259-014-9621-2pubmed: 25417198google scholar: lookup
  44. Turnquist HR, Cardinal J, Macedo C, Rosborough BR, Sumpter TL, Geller DA, Metes D, Thomson AW. mTOR and GSK-3 shape the CD4+ T-cell stimulatory and differentiation capacity of myeloid DCs after exposure to LPS.. Blood 2010 Jun 10;115(23):4758-69.
    doi: 10.1182/blood-2009-10-251488pmc: PMC2890188pubmed: 20335217google scholar: lookup
  45. Deifl S, Kitzmüller C, Steinberger P, Himly M, Jahn-Schmid B, Fischer GF, Zlabinger GJ, Bohle B. Differential activation of dendritic cells by toll-like receptors causes diverse differentiation of naïve CD4+ T cells from allergic patients.. Allergy 2014 Dec;69(12):1602-9.
    doi: 10.1111/all.12501pmc: PMC4245478pubmed: 25093709google scholar: lookup
  46. Libermann TA, Baltimore D. Activation of interleukin-6 gene expression through the NF-kappa B transcription factor.. Mol Cell Biol 1990 May;10(5):2327-34.
    doi: 10.1128/MCB.10.5.2327pmc: PMC360580pubmed: 2183031google scholar: lookup
  47. Wang C, Gong B, Bushel PR, Thierry-Mieg J, Thierry-Mieg D, Xu J, Fang H, Hong H, Shen J, Su Z, Meehan J, Li X, Yang L, Li H, Łabaj PP, Kreil DP, Megherbi D, Gaj S, Caiment F, van Delft J, Kleinjans J, Scherer A, Devanarayan V, Wang J, Yang Y, Qian HR, Lancashire LJ, Bessarabova M, Nikolsky Y, Furlanello C, Chierici M, Albanese D, Jurman G, Riccadonna S, Filosi M, Visintainer R, Zhang KK, Li J, Hsieh JH, Svoboda DL, Fuscoe JC, Deng Y, Shi L, Paules RS, Auerbach SS, Tong W. The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance.. Nat Biotechnol 2014 Sep;32(9):926-32.
    doi: 10.1038/nbt.3001pmc: PMC4243706pubmed: 25150839google scholar: lookup
  48. Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data.. Genome Biol 2010;11(3):R25.
    doi: 10.1186/gb-2010-11-3-r25pmc: PMC2864565pubmed: 20196867google scholar: lookup
  49. Bullard JH, Purdom E, Hansen KD, Dudoit S. Evaluation of statistical methods for normalization and differential expression in mRNA-Seq experiments.. BMC Bioinformatics 2010 Feb 18;11:94.
    doi: 10.1186/1471-2105-11-94pmc: PMC2838869pubmed: 20167110google scholar: lookup
  50. Sood A, Petersen H, Blanchette CM, Meek P, Picchi MA, Belinsky SA, Tesfaigzi Y. Methylated Genes in Sputum Among Older Smokers With Asthma.. Chest 2012 Aug;142(2):425-431.
    doi: 10.1378/chest.11-2519pmc: PMC3425338pubmed: 22345380google scholar: lookup
  51. Fehr AR, Yu D. Control the host cell cycle: viral regulation of the anaphase-promoting complex.. J Virol 2013 Aug;87(16):8818-25.
    doi: 10.1128/JVI.00088-13pmc: PMC3754035pubmed: 23760246google scholar: lookup
  52. Castro A, Bernis C, Vigneron S, Labbé JC, Lorca T. The anaphase-promoting complex: a key factor in the regulation of cell cycle.. Oncogene 2005 Jan 13;24(3):314-25.
    doi: 10.1038/sj.onc.1207973pubmed: 15678131google scholar: lookup
  53. Wäsch R, Engelbert D. Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells.. Oncogene 2005 Jan 6;24(1):1-10.
    doi: 10.1038/sj.onc.1208017pubmed: 15637585google scholar: lookup
  54. Nakayama T. Immune-specific production of gamma interferon in human lymphocyte cultures in response to mumps virus.. Infect Immun 1983 May;40(2):486-92.
    pmc: PMC264881pubmed: 6404827doi: 10.1128/iai.40.2.486-492.1983google scholar: lookup
  55. Green JA, Cooperband SR, Kibrick S. Immune specific induction of interferon production in cultures of human blood lymphocytes.. Science 1969 Jun 20;164(3886):1415-7.
    doi: 10.1126/science.164.3886.1415pubmed: 5783715google scholar: lookup
  56. Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive immune responses.. Adv Immunol 2007;96:41-101.
    doi: 10.1016/S0065-2776(07)96002-2pubmed: 17981204google scholar: lookup
  57. Gerard NP, Gerard C. Complement in allergy and asthma.. Curr Opin Immunol 2002 Dec;14(6):705-8.
    doi: 10.1016/S0952-7915(02)00410-7pubmed: 12413519google scholar: lookup
  58. Lajoie S, Lewkowich IP, Suzuki Y, Clark JR, Sproles AA, Dienger K, Budelsky AL, Wills-Karp M. Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma.. Nat Immunol 2010 Oct;11(10):928-35.
    doi: 10.1038/ni.1926pmc: PMC2943538pubmed: 20802484google scholar: lookup
  59. Köhl J, Wills-Karp M. A dual role for complement in allergic asthma.. Curr Opin Pharmacol 2007 Jun;7(3):283-9.
    doi: 10.1016/j.coph.2007.01.005pubmed: 17475559google scholar: lookup
  60. Karp CL, Grupe A, Schadt E, Ewart SL, Keane-Moore M, Cuomo PJ, Köhl J, Wahl L, Kuperman D, Germer S, Aud D, Peltz G, Wills-Karp M. Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma.. Nat Immunol 2000 Sep;1(3):221-6.
    doi: 10.1038/79759pubmed: 10973279google scholar: lookup
  61. Zhang X, Köhl J. A complex role for complement in allergic asthma.. Expert Rev Clin Immunol 2010 Mar;6(2):269-77.
    doi: 10.1586/eci.09.84pmc: PMC2856962pubmed: 20402389google scholar: lookup
  62. Lin H, Lee E, Hestir K, Leo C, Huang M, Bosch E, Halenbeck R, Wu G, Zhou A, Behrens D, Hollenbaugh D, Linnemann T, Qin M, Wong J, Chu K, Doberstein SK, Williams LT. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome.. Science 2008 May 9;320(5877):807-11.
    doi: 10.1126/science.1154370pubmed: 18467591google scholar: lookup
  63. Wang Y, Colonna M. Interkeukin-34, a cytokine crucial for the differentiation and maintenance of tissue resident macrophages and Langerhans cells.. Eur J Immunol 2014 Jun;44(6):1575-81.
    doi: 10.1002/eji.201344365pmc: PMC4137395pubmed: 24737461google scholar: lookup
  64. Masteller EL, Wong BR. Targeting IL-34 in chronic inflammation.. Drug Discov Today 2014 Aug;19(8):1212-6.
    doi: 10.1016/j.drudis.2014.05.016pubmed: 24906044google scholar: lookup
  65. Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1).. J Exp Med 1996 Sep 1;184(3):1101-9.
    doi: 10.1084/jem.184.3.1101pmc: PMC2192798pubmed: 9064327google scholar: lookup
  66. Augsten M, Hägglöf C, Olsson E, Stolz C, Tsagozis P, Levchenko T, Frederick MJ, Borg A, Micke P, Egevad L, Ostman A. CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth.. Proc Natl Acad Sci U S A 2009 Mar 3;106(9):3414-9.
    doi: 10.1073/pnas.0813144106pmc: PMC2651265pubmed: 19218429google scholar: lookup
  67. Schulz-Knappe P, Mägert HJ, Dewald B, Meyer M, Cetin Y, Kubbies M, Tomeczkowski J, Kirchhoff K, Raida M, Adermann K, Kist A, Reinecke M, Sillard R, Pardigol A, Uguccioni M, Baggiolini M, Forssmann WG. HCC-1, a novel chemokine from human plasma.. J Exp Med 1996 Jan 1;183(1):295-9.
    doi: 10.1084/jem.183.1.295pmc: PMC2192403pubmed: 8551235google scholar: lookup
  68. Blain KY, Kwiatkowski W, Zhao Q, La Fleur D, Naik C, Chun TW, Tsareva T, Kanakaraj P, Laird MW, Shah R, George L, Sanyal I, Moore PA, Demeler B, Choe S. Structural and functional characterization of CC chemokine CCL14.. Biochemistry 2007 Sep 4;46(35):10008-15.
    doi: 10.1021/bi700936wpubmed: 17691823google scholar: lookup
  69. Ansel KM, Ngo VN, Hyman PL, Luther SA, Förster R, Sedgwick JD, Browning JL, Lipp M, Cyster JG. A chemokine-driven positive feedback loop organizes lymphoid follicles.. Nature 2000 Jul 20;406(6793):309-14.
    doi: 10.1038/35018581pubmed: 10917533google scholar: lookup
  70. Carlsen HS, Baekkevold ES, Morton HC, Haraldsen G, Brandtzaeg P. Monocyte-like and mature macrophages produce CXCL13 (B cell-attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis.. Blood 2004 Nov 15;104(10):3021-7.
    doi: 10.1182/blood-2004-02-0701pubmed: 15284119google scholar: lookup
  71. Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.. J Exp Med 1989 Dec 1;170(6):2081-95.
    doi: 10.1084/jem.170.6.2081pmc: PMC2189521pubmed: 2531194google scholar: lookup
  72. Klier J, May A, Fuchs S, Schillinger U, Plank C, Winter G, Gehlen H, Coester C. Immunostimulation of bronchoalveolar lavage cells from recurrent airway obstruction-affected horses by different CpG-classes bound to gelatin nanoparticles.. Vet Immunol Immunopathol 2011 Nov 15;144(1-2):79-87.
    doi: 10.1016/j.vetimm.2011.07.009pubmed: 21831455google scholar: lookup
  73. Hamza E, Wagner B, Jungi TW, Mirkovitch J, Marti E. Reduced incidence of insect-bite hypersensitivity in Icelandic horses is associated with a down-regulation of interleukin-4 by interleukin-10 and transforming growth factor-beta1.. Vet Immunol Immunopathol 2008 Mar 15;122(1-2):65-75.
    doi: 10.1016/j.vetimm.2007.10.018pubmed: 18082270google scholar: lookup
  74. Takagi R, Higashi T, Hashimoto K, Nakano K, Mizuno Y, Okazaki Y, Matsushita S. B cell chemoattractant CXCL13 is preferentially expressed by human Th17 cell clones.. J Immunol 2008 Jul 1;181(1):186-9.
    pubmed: 18566383doi: 10.4049/jimmunol.181.1.186google scholar: lookup
  75. Singh RP, Hasan S, Sharma S, Nagra S, Yamaguchi DT, Wong DT, Hahn BH, Hossain A. Th17 cells in inflammation and autoimmunity.. Autoimmun Rev 2014 Dec;13(12):1174-81.
    doi: 10.1016/j.autrev.2014.08.019pubmed: 25151974google scholar: lookup
  76. Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagé N, Olivenstein R, Elias J, Chakir J. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines.. J Allergy Clin Immunol 2001 Sep;108(3):430-8.
    doi: 10.1067/mai.2001.117929pubmed: 11544464google scholar: lookup
  77. Wang Q, Li H, Yao Y, Xia D, Zhou J. The overexpression of heparin-binding epidermal growth factor is responsible for Th17-induced airway remodeling in an experimental asthma model.. J Immunol 2010 Jul 15;185(2):834-41.
    doi: 10.4049/jimmunol.0901490pubmed: 20530256google scholar: lookup
  78. Tello D, Balsa E, Acosta-Iborra B, Fuertes-Yebra E, Elorza A, Ordóñez Á, Corral-Escariz M, Soro I, López-Bernardo E, Perales-Clemente E, Martínez-Ruiz A, Enríquez JA, Aragonés J, Cadenas S, Landázuri MO. Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting Complex I activity.. Cell Metab 2011 Dec 7;14(6):768-79.
    doi: 10.1016/j.cmet.2011.10.008pubmed: 22100406google scholar: lookup
  79. Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P. Increased hypoxia-inducible factor 1α expression in lung cells of horses with recurrent airway obstruction.. BMC Vet Res 2012 May 23;8:64.
    doi: 10.1186/1746-6148-8-64pmc: PMC3536633pubmed: 22621400google scholar: lookup
  80. Huerta-Yepez S, Baay-Guzman GJ, Bebenek IG, Hernandez-Pando R, Vega MI, Chi L, Riedl M, Diaz-Sanchez D, Kleerup E, Tashkin DP, Gonzalez FJ, Bonavida B, Zeidler M, Hankinson O. Hypoxia inducible factor promotes murine allergic airway inflammation and is increased in asthma and rhinitis.. Allergy 2011 Jul;66(7):909-18.
    doi: 10.1111/j.1398-9995.2011.02594.xpmc: PMC3107385pubmed: 21517900google scholar: lookup
  81. Nishi H, Nakada T, Kyo S, Inoue M, Shay JW, Isaka K. Hypoxia-inducible factor 1 mediates upregulation of telomerase (hTERT).. Mol Cell Biol 2004 Jul;24(13):6076-83.
    doi: 10.1128/MCB.24.13.6076-6083.2004pmc: PMC480902pubmed: 15199161google scholar: lookup
  82. Schödel J, Oikonomopoulos S, Ragoussis J, Pugh CW, Ratcliffe PJ, Mole DR. High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq.. Blood 2011 Jun 9;117(23):e207-17.
    doi: 10.1182/blood-2010-10-314427pmc: PMC3374576pubmed: 21447827google scholar: lookup
  83. Xia X, Kung AL. Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia.. Genome Biol 2009;10(10):R113.
    doi: 10.1186/gb-2009-10-10-r113pmc: PMC2784328pubmed: 19828020google scholar: lookup
  84. Portales-Casamar E, Arenillas D, Lim J, Swanson MI, Jiang S, McCallum A, Kirov S, Wasserman WW. The PAZAR database of gene regulatory information coupled to the ORCA toolkit for the study of regulatory sequences.. Nucleic Acids Res 2009 Jan;37(Database issue):D54-60.
    doi: 10.1093/nar/gkn783pmc: PMC2686574pubmed: 18971253google scholar: lookup
  85. Waddell JA, Emerson PA, Gunstone RF. Hypoxia in bronchial asthma.. Br Med J 1967 May 13;2(5549):402-4.
    doi: 10.1136/bmj.2.5549.402pmc: PMC1845095pubmed: 6022033google scholar: lookup
  86. McFadden ER Jr, Lyons HA. Arterial-blood gas tension in asthma.. N Engl J Med 1968 May 9;278(19):1027-32.
    doi: 10.1056/NEJM196805092781901pubmed: 5644962google scholar: lookup
  87. Simpson H, Forfar JO, Grubb DJ. Arterial blood gas tensions and pH in acute asthma in childhood.. Br Med J 1968 Aug 24;3(5616):460-4.
    doi: 10.1136/bmj.3.5616.460pmc: PMC1986374pubmed: 5666802google scholar: lookup
  88. Nizet V, Johnson RS. Interdependence of hypoxic and innate immune responses.. Nat Rev Immunol 2009 Sep;9(9):609-17.
    doi: 10.1038/nri2607pmc: PMC4343208pubmed: 19704417google scholar: lookup
  89. Eltzschig HK, Carmeliet P. Hypoxia and inflammation.. N Engl J Med 2011 Feb 17;364(7):656-65.
    doi: 10.1056/NEJMra0910283pmc: PMC3930928pubmed: 21323543google scholar: lookup
  90. Baek KJ, Cho JY, Rosenthal P, Alexander LEC, Nizet V, Broide DH. Hypoxia potentiates allergen induction of HIF-1α, chemokines, airway inflammation, TGF-β1, and airway remodeling in a mouse model.. Clin Immunol 2013 Apr;147(1):27-37.
    doi: 10.1016/j.clim.2013.02.004pmc: PMC3812068pubmed: 23499929google scholar: lookup
  91. Ahmad T, Kumar M, Mabalirajan U, Pattnaik B, Aggarwal S, Singh R, Singh S, Mukerji M, Ghosh B, Agrawal A. Hypoxia response in asthma: differential modulation on inflammation and epithelial injury.. Am J Respir Cell Mol Biol 2012 Jul;47(1):1-10.
    doi: 10.1165/rcmb.2011-0203OCpubmed: 22312019google scholar: lookup
  92. Guo J, Lu W, Shimoda LA, Semenza GL, Georas SN. Enhanced interferon-gamma gene expression in T Cells and reduced ovalbumin-dependent lung eosinophilia in hypoxia-inducible factor-1-alpha-deficient mice.. Int Arch Allergy Immunol 2009;149(2):98-102.
    doi: 10.1159/000189191pmc: PMC2824623pubmed: 19127065google scholar: lookup
  93. Kallio PJ, Okamoto K, O'Brien S, Carrero P, Makino Y, Tanaka H, Poellinger L. Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha.. EMBO J 1998 Nov 16;17(22):6573-86.
    doi: 10.1093/emboj/17.22.6573pmc: PMC1171004pubmed: 9822602google scholar: lookup
  94. van Uden P, Kenneth NS, Rocha S. Regulation of hypoxia-inducible factor-1alpha by NF-kappaB.. Biochem J 2008 Jun 15;412(3):477-84.
    doi: 10.1042/BJ20080476pmc: PMC2474706pubmed: 18393939google scholar: lookup
  95. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, Johnson RS, Haddad GG, Karin M. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha.. Nature 2008 Jun 5;453(7196):807-11.
    doi: 10.1038/nature06905pmc: PMC2669289pubmed: 18432192google scholar: lookup
  96. McMahon S, Charbonneau M, Grandmont S, Richard DE, Dubois CM. Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression.. J Biol Chem 2006 Aug 25;281(34):24171-81.
    doi: 10.1074/jbc.M604507200pubmed: 16815840google scholar: lookup
  97. Blouin CC, Pagé EL, Soucy GM, Richard DE. Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1alpha.. Blood 2004 Feb 1;103(3):1124-30.
    doi: 10.1182/blood-2003-07-2427pubmed: 14525767google scholar: lookup
  98. Poynter ME, Cloots R, van Woerkom T, Butnor KJ, Vacek P, Taatjes DJ, Irvin CG, Janssen-Heininger YM. NF-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness.. J Immunol 2004 Dec 1;173(11):7003-9.
    doi: 10.4049/jimmunol.173.11.7003pmc: PMC2830271pubmed: 15557197google scholar: lookup
  99. Tang ML, Wilson JW, Stewart AG, Royce SG. Airway remodelling in asthma: current understanding and implications for future therapies.. Pharmacol Ther 2006 Nov;112(2):474-88.
    doi: 10.1016/j.pharmthera.2006.05.001pubmed: 16759709google scholar: lookup
  100. Dalton JE, Pearson J, Scott P, Carding SR. The interaction of gamma delta T cells with activated macrophages is a property of the V gamma 1 subset.. J Immunol 2003 Dec 15;171(12):6488-94.
    pubmed: 14662848doi: 10.4049/jimmunol.171.12.6488google scholar: lookup
  101. Dalton JE, Howell G, Pearson J, Scott P, Carding SR. Fas-Fas ligand interactions are essential for the binding to and killing of activated macrophages by gamma delta T cells.. J Immunol 2004 Sep 15;173(6):3660-7.
    pubmed: 15356111doi: 10.4049/jimmunol.173.6.3660google scholar: lookup
  102. Turlej RK, Fiévez L, Sandersen CF, Dogné S, Kirschvink N, Lekeux P, Bureau F. Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway.. Thorax 2001 Sep;56(9):696-702.
    doi: 10.1136/thorax.56.9.696pmc: PMC1746130pubmed: 11514690google scholar: lookup
  103. Niedzwiedz A, Jaworski Z, Tykalowski B, Smialek M. Neutrophil and macrophage apoptosis in bronchoalveolar lavage fluid from healthy horses and horses with recurrent airway obstruction (RAO).. BMC Vet Res 2014 Jan 24;10:29.
    doi: 10.1186/1746-6148-10-29pmc: PMC3903020pubmed: 24460911google scholar: lookup
  104. Wu MX, Ao Z, Prasad KV, Wu R, Schlossman SF. IEX-1L, an apoptosis inhibitor involved in NF-kappaB-mediated cell survival.. Science 1998 Aug 14;281(5379):998-1001.
    doi: 10.1126/science.281.5379.998pubmed: 9703517google scholar: lookup
  105. Schott J, Reitter S, Philipp J, Haneke K, Schäfer H, Stoecklin G. Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation.. PLoS Genet 2014 Jun;10(6):e1004368.
    doi: 10.1371/journal.pgen.1004368pmc: PMC4063670pubmed: 24945926google scholar: lookup
  106. Jiang J, Jedinak A, Sliva D. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA.. Biochem Biophys Res Commun 2011 Nov 18;415(2):325-9.
    doi: 10.1016/j.bbrc.2011.10.055pubmed: 22033405google scholar: lookup
  107. Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M. Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients.. J Surg Oncol 2012 Sep 15;106(4):423-30.
    doi: 10.1002/jso.23109pubmed: 22488197google scholar: lookup
  108. Huang HC, Shi J, Orth JD, Mitchison TJ. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly.. Cancer Cell 2009 Oct 6;16(4):347-58.
    doi: 10.1016/j.ccr.2009.08.020pmc: PMC2758291pubmed: 19800579google scholar: lookup
  109. Kidokoro T, Tanikawa C, Furukawa Y, Katagiri T, Nakamura Y, Matsuda K. CDC20, a potential cancer therapeutic target, is negatively regulated by p53.. Oncogene 2008 Mar 6;27(11):1562-71.
    doi: 10.1038/sj.onc.1210799pubmed: 17873905google scholar: lookup
  110. Wan L, Tan M, Yang J, Inuzuka H, Dai X, Wu T, Liu J, Shaik S, Chen G, Deng J, Malumbres M, Letai A, Kirschner MW, Sun Y, Wei W. APC(Cdc20) suppresses apoptosis through targeting Bim for ubiquitination and destruction.. Dev Cell 2014 May 27;29(4):377-91.
    doi: 10.1016/j.devcel.2014.04.022pmc: PMC4081014pubmed: 24871945google scholar: lookup
  111. Zasłona Z, Przybranowski S, Wilke C, van Rooijen N, Teitz-Tennenbaum S, Osterholzer JJ, Wilkinson JE, Moore BB, Peters-Golden M. Resident alveolar macrophages suppress, whereas recruited monocytes promote, allergic lung inflammation in murine models of asthma.. J Immunol 2014 Oct 15;193(8):4245-53.
    doi: 10.4049/jimmunol.1400580pmc: PMC4185233pubmed: 25225663google scholar: lookup
  112. Voelkel NF, Spiegel S. Why is effective treatment of asthma so difficult? An integrated systems biology hypothesis of asthma.. Immunol Cell Biol 2009 Nov-Dec;87(8):601-5.
    doi: 10.1038/icb.2009.45pmc: PMC2850593pubmed: 19546879google scholar: lookup
  113. Mo JH, Kim JH, Lim DJ, Kim EH. The role of hypoxia-inducible factor 1α in allergic rhinitis.. Am J Rhinol Allergy 2014 Mar-Apr;28(2):e100-6.
    doi: 10.2500/ajra.2014.28.4025pubmed: 24717944google scholar: lookup
  114. Baay-Guzman GJ, Huerta-Yepez S, Vega MI, Aguilar-Leon D, Campillos M, Blake J, Benes V, Hernandez-Pando R, Teran LM. Role of CXCL13 in asthma: novel therapeutic target.. Chest 2012 Apr;141(4):886-894.
    doi: 10.1378/chest.11-0633pubmed: 22016489google scholar: lookup
  115. Festa ED, Hankiewicz K, Kim S, Skurnick J, Wolansky LJ, Cook SD, Cadavid D. Serum levels of CXCL13 are elevated in active multiple sclerosis.. Mult Scler 2009 Nov;15(11):1271-9.
    doi: 10.1177/1352458509107017pubmed: 19805441google scholar: lookup
  116. Meraouna A, Cizeron-Clairac G, Panse RL, Bismuth J, Truffault F, Tallaksen C, Berrih-Aknin S. The chemokine CXCL13 is a key molecule in autoimmune myasthenia gravis.. Blood 2006 Jul 15;108(2):432-40.
    doi: 10.1182/blood-2005-06-2383pmc: PMC1847364pubmed: 16543475google scholar: lookup
  117. Hansen S, Baptiste KE, Fjeldborg J, Betancourt A, Horohov DW. A comparison of pro-inflammatory cytokine mRNA expression in equine bronchoalveolar lavage (BAL) and peripheral blood.. Vet Immunol Immunopathol 2014 Apr 15;158(3-4):238-43.
    doi: 10.1016/j.vetimm.2014.02.001pubmed: 24603016google scholar: lookup
  118. Lindberg A, Robinson NE, Näsman-Glaser B, Jensen-Waern M, Lindgren JA. Assessment of leukotriene B4 production in leukocytes from horses with recurrent airway obstruction.. Am J Vet Res 2004 Mar;65(3):289-95.
    doi: 10.2460/ajvr.2004.65.289pubmed: 15027674google scholar: lookup
  119. Henríquez C, Perez B, Morales N, Sarmiento J, Carrasco C, Morán G, Folch H. Participation of T regulatory cells in equine recurrent airway obstruction.. Vet Immunol Immunopathol 2014 Apr 15;158(3-4):128-34.
    doi: 10.1016/j.vetimm.2013.12.005pubmed: 24503328google scholar: lookup
  120. Sarmiento J, Perez B, Morales N, Henriquez C, Vidal L, Folch H, Galecio JS, Morán G. Apoptotic effects of tamoxifen on leukocytes from horse peripheral blood and bronchoalveolar lavage fluid.. Vet Res Commun 2013 Dec;37(4):333-8.
    doi: 10.1007/s11259-013-9571-0pubmed: 23846832google scholar: lookup

Citations

This article has been cited 19 times.
  1. Sage SE, Nicholson P, Leeb T, Gerber V, Jagannathan V. Long-Read Transcriptome of Equine Bronchoalveolar Cells. Genes (Basel) 2022 Sep 25;13(10).
    doi: 10.3390/genes13101722pubmed: 36292607google scholar: lookup
  2. Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing. Animals (Basel) 2022 Mar 16;12(6).
    doi: 10.3390/ani12060744pubmed: 35327141google scholar: lookup
  3. Alashkar Alhamwe B, Potaczek DP, Miethe S, Alhamdan F, Hintz L, Magomedov A, Garn H. Extracellular Vesicles and Asthma-More Than Just a Co-Existence. Int J Mol Sci 2021 May 7;22(9).
    doi: 10.3390/ijms22094984pubmed: 34067156google scholar: lookup
  4. Hulliger MF, Pacholewska A, Vargas A, Lavoie JP, Leeb T, Gerber V, Jagannathan V. An Integrative miRNA-mRNA Expression Analysis Reveals Striking Transcriptomic Similarities between Severe Equine Asthma and Specific Asthma Endotypes in Humans. Genes (Basel) 2020 Sep 28;11(10).
    doi: 10.3390/genes11101143pubmed: 32998415google scholar: lookup
  5. Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP, Martin J, Moran G, Niedźwiedź A, Pusterla N, Swiderski C. Equine Asthma: Current Understanding and Future Directions. Front Vet Sci 2020;7:450.
    doi: 10.3389/fvets.2020.00450pubmed: 32903600google scholar: lookup
  6. Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era. Anim Genet 2019 Dec;50(6):569-597.
    doi: 10.1111/age.12857pubmed: 31568563google scholar: lookup
  7. Saini S, Singha H, Siwach P, Tripathi BN. Recombinant horse interleukin-4 and interleukin-10 induced a mixed inflammatory cytokine response in horse peripheral blood mononuclear cells. Vet World 2019;12(4):496-503.
    doi: 10.14202/vetworld.2019.496-503pubmed: 31190704google scholar: lookup
  8. Davis KU, Sheats MK. Bronchoalveolar Lavage Cytology Characteristics and Seasonal Changes in a Herd of Pastured Teaching Horses. Front Vet Sci 2019;6:74.
    doi: 10.3389/fvets.2019.00074pubmed: 30923711google scholar: lookup
  9. Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. Gene set enrichment analysis of the bronchial epithelium implicates contribution of cell cycle and tissue repair processes in equine asthma. Sci Rep 2018 Nov 6;8(1):16408.
    doi: 10.1038/s41598-018-34636-9pubmed: 30401798google scholar: lookup
  10. Bond S, Léguillette R, Richard EA, Couetil L, Lavoie JP, Martin JG, Pirie RS. Equine asthma: Integrative biologic relevance of a recently proposed nomenclature. J Vet Intern Med 2018 Nov;32(6):2088-2098.
    doi: 10.1111/jvim.15302pubmed: 30294851google scholar: lookup
  11. Mason VC, Schaefer RJ, McCue ME, Leeb T, Gerber V. eQTL discovery and their association with severe equine asthma in European Warmblood horses. BMC Genomics 2018 Aug 2;19(1):581.
    doi: 10.1186/s12864-018-4938-9pubmed: 30071827google scholar: lookup
  12. Pacholewska A, Kraft MF, Gerber V, Jagannathan V. Differential Expression of Serum MicroRNAs Supports CD4⁺ T Cell Differentiation into Th2/Th17 Cells in Severe Equine Asthma. Genes (Basel) 2017 Dec 12;8(12).
    doi: 10.3390/genes8120383pubmed: 29231896google scholar: lookup
  13. Aun MV, Bonamichi-Santos R, Arantes-Costa FM, Kalil J, Giavina-Bianchi P. Animal models of asthma: utility and limitations. J Asthma Allergy 2017;10:293-301.
    doi: 10.2147/JAA.S121092pubmed: 29158683google scholar: lookup
  14. Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma. BMC Genomics 2017 Sep 8;18(1):708.
    doi: 10.1186/s12864-017-4107-6pubmed: 28886691google scholar: lookup
  15. Pacholewska A, Marti E, Leeb T, Jagannathan V, Gerber V. LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells. BMC Genomics 2017 Jan 5;18(1):34.
    doi: 10.1186/s12864-016-3390-ypubmed: 28056766google scholar: lookup
  16. Niedzwiedz A, Borowicz H, Januszewska L, Markiewicz-Gorka I, Jaworski Z. Serum 8-hydroxy-2-deoxyguanosine as a marker of DNA oxidative damage in horses with recurrent airway obstruction. Acta Vet Scand 2016 Jun 7;58(1):38.
    doi: 10.1186/s13028-016-0215-6pubmed: 27267076google scholar: lookup
  17. Dlugopolska D, Siwinska N, Noszczyk-Nowak A. Equine Asthma in a Comparative Perspective: Cardiovascular and Neurological Manifestations of Asthma Across Different Species. Animals (Basel) 2025 Aug 12;15(16).
    doi: 10.3390/ani15162371pubmed: 40867700google scholar: lookup
  18. Simões J, Tilley P. Decision Making in Severe Equine Asthma-Diagnosis and Monitoring. Animals (Basel) 2023 Dec 16;13(24).
    doi: 10.3390/ani13243872pubmed: 38136909google scholar: lookup
  19. Riihimäki M, Fegraeus K, Nordlund J, Waern I, Wernersson S, Akula S, Hellman L, Raine A. Single-cell transcriptomics delineates the immune cell landscape in equine lower airways and reveals upregulation of FKBP5 in horses with asthma. Sci Rep 2023 Sep 27;13(1):16261.
    doi: 10.1038/s41598-023-43368-4pubmed: 37758813google scholar: lookup
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