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.
Publication Date: 2015-08-20 PubMed ID: 26292153PubMed Central: PMC4546272DOI: 10.1371/journal.pone.0136103Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- 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, Dru00f6gemu00fcller M, Klukowska-Ru00f6tzler 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
Researcher Affiliations
- Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- 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.
- Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.
- 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.
- 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.
- Clinical Immunology Group, Department of Clinical Research and Veterinary Public Health, University of Bern, Bern, Switzerland.
- Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- 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
- Ansotegui I, Arruda LKP, Badellino HA, Baena-Cagnani CE, Bahna SL, Baldacci S, et al. White Book on Allergy: Update 2013. Pawankar R, Holgate ST, Canonica GW, Lockey RF, Blaiss MS, editors. Milwaukee: World Allergy Organization (WAO); 2013.
- Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches.. Nat Med 2012 May 4;18(5):716-25.
- 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.
- Edfors-Lubs ML. Allergy in 7000 twin pairs.. Acta Allergol 1971 Aug;26(4):249-85.
- 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.
- Temesi G, Viru00e1g V, Hadadi E, Ungvu00e1ri I, Fodor LE, Bikov A, Nagy A, Gu00e1lffy G, Tamu00e1si L, Horvu00e1th I, Kiss A, Hullu00e1m G, Gu00e9zsi A, Su00e1rku00f6zy P, Antal P, Buzu00e1s 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.
- 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.
- Mullane K, Williams M. Animal models of asthma: reprise or reboot?. Biochem Pharmacol 2014 Jan 1;87(1):131-9.
- Moran G, Folch H. Recurrent airway obstruction in horsesu2014An allergic inflammation: A review. Vet Med (Praha). 2011;56: 1u201313.
- Bru00fcndler 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.
- Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011 Oct;16(7):1027-46.
- 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.
- 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.
- Swinburne JE, Bogle H, Klukowska-Ru00f6tzler J, Dru00f6gemu00fcller 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.
- 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.
- 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.
- Gerber V, Baleri D, Klukowska-Ru00f6tzler J, Swinburne JE, Dolf G. Mixed inheritance of equine recurrent airway obstruction.. J Vet Intern Med 2009 May-Jun;23(3):626-30.
- Lanz S, Gerber V, Marti E, Rettmer H, Klukowska-Ru00f6tzler 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.
- 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.
- Klukowska-Ru00f6tzler J, Swinburne JE, Dru00f6gemu00fcller 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.
- 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.
- 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.
- 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.
- Jost U, Klukowska-Ru00f6tzler 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.
- 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.
- 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.
- 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.
- Pacholewska A, Dru00f6gemu00fcller M, Klukowska-Ru00f6tzler 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.
- 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.
- 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.
- 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.
- 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.
- Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blu00f6cker 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, Guu00e9rin 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, Ru00f8ed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvu00e4nen 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.
- 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.
- Anders S, Huber W. Differential expression analysis for sequence count data.. Genome Biol 2010;11(10):R106.
- 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.
- 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.
- 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.
- 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.
- 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.
- Kinsella RJ, Ku00e4hu00e4ri 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.
- 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.
- 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.
- 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.
- Deifl S, Kitzmu00fcller 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 nau00efve CD4+ T cells from allergic patients.. Allergy 2014 Dec;69(12):1602-9.
- 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.
- 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, u0141abaj 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.
- Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data.. Genome Biol 2010;11(3):R25.
- 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.
- 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.
- Fehr AR, Yu D. Control the host cell cycle: viral regulation of the anaphase-promoting complex.. J Virol 2013 Aug;87(16):8818-25.
- Castro A, Bernis C, Vigneron S, Labbu00e9 JC, Lorca T. The anaphase-promoting complex: a key factor in the regulation of cell cycle.. Oncogene 2005 Jan 13;24(3):314-25.
- Wu00e4sch 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.
- 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.
- 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.
- Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive immune responses.. Adv Immunol 2007;96:41-101.
- Gerard NP, Gerard C. Complement in allergy and asthma.. Curr Opin Immunol 2002 Dec;14(6):705-8.
- 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.
- Ku00f6hl J, Wills-Karp M. A dual role for complement in allergic asthma.. Curr Opin Pharmacol 2007 Jun;7(3):283-9.
- Karp CL, Grupe A, Schadt E, Ewart SL, Keane-Moore M, Cuomo PJ, Ku00f6hl 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.
- Zhang X, Ku00f6hl J. A complex role for complement in allergic asthma.. Expert Rev Clin Immunol 2010 Mar;6(2):269-77.
- 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.
- 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.
- Masteller EL, Wong BR. Targeting IL-34 in chronic inflammation.. Drug Discov Today 2014 Aug;19(8):1212-6.
- 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.
- Augsten M, Hu00e4gglu00f6f 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.
- Schulz-Knappe P, Mu00e4gert 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.
- 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.
- Ansel KM, Ngo VN, Hyman PL, Luther SA, Fu00f6rster 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagu00e9 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.
- 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.
- Tello D, Balsa E, Acosta-Iborra B, Fuertes-Yebra E, Elorza A, Ordu00f3u00f1ez u00c1, Corral-Escariz M, Soro I, Lu00f3pez-Bernardo E, Perales-Clemente E, Martu00ednez-Ruiz A, Enru00edquez JA, Aragonu00e9s J, Cadenas S, Landu00e1zuri MO. Induction of the mitochondrial NDUFA4L2 protein by HIF-1u03b1 decreases oxygen consumption by inhibiting Complex I activity.. Cell Metab 2011 Dec 7;14(6):768-79.
- Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P. Increased hypoxia-inducible factor 1u03b1 expression in lung cells of horses with recurrent airway obstruction.. BMC Vet Res 2012 May 23;8:64.
- 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.
- 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.
- Schu00f6del 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.
- 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.
- 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.
- Waddell JA, Emerson PA, Gunstone RF. Hypoxia in bronchial asthma.. Br Med J 1967 May 13;2(5549):402-4.
- McFadden ER Jr, Lyons HA. Arterial-blood gas tension in asthma.. N Engl J Med 1968 May 9;278(19):1027-32.
- 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.
- Nizet V, Johnson RS. Interdependence of hypoxic and innate immune responses.. Nat Rev Immunol 2009 Sep;9(9):609-17.
- Eltzschig HK, Carmeliet P. Hypoxia and inflammation.. N Engl J Med 2011 Feb 17;364(7):656-65.
- Baek KJ, Cho JY, Rosenthal P, Alexander LEC, Nizet V, Broide DH. Hypoxia potentiates allergen induction of HIF-1u03b1, chemokines, airway inflammation, TGF-u03b21, and airway remodeling in a mouse model.. Clin Immunol 2013 Apr;147(1):27-37.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Blouin CC, Pagu00e9 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.
- 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.
- 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.
- 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.
- 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.
- Turlej RK, Fiu00e9vez L, Sandersen CF, Dognu00e9 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.
- 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.
- 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.
- Schott J, Reitter S, Philipp J, Haneke K, Schu00e4fer H, Stoecklin G. Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation.. PLoS Genet 2014 Jun;10(6):e1004368.
- 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.
- 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.
- 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.
- 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.
- 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.
- Zasu0142ona 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.
- 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.
- Mo JH, Kim JH, Lim DJ, Kim EH. The role of hypoxia-inducible factor 1u03b1 in allergic rhinitis.. Am J Rhinol Allergy 2014 Mar-Apr;28(2):e100-6.
- 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.
- 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.
- 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.
- 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.
- Lindberg A, Robinson NE, Nu00e4sman-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.
- Henru00edquez C, Perez B, Morales N, Sarmiento J, Carrasco C, Moru00e1n G, Folch H. Participation of T regulatory cells in equine recurrent airway obstruction.. Vet Immunol Immunopathol 2014 Apr 15;158(3-4):128-34.
- Sarmiento J, Perez B, Morales N, Henriquez C, Vidal L, Folch H, Galecio JS, Moru00e1n G. Apoptotic effects of tamoxifen on leukocytes from horse peripheral blood and bronchoalveolar lavage fluid.. Vet Res Commun 2013 Dec;37(4):333-8.
Citations
This article has been cited 16 times.- Sage SE, Nicholson P, Leeb T, Gerber V, Jagannathan V. Long-Read Transcriptome of Equine Bronchoalveolar Cells.. Genes (Basel) 2022 Sep 25;13(10).
- Simu00f5es 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).
- 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).
- 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).
- Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP, Martin J, Moran G, Niedu017awiedu017a A, Pusterla N, Swiderski C. Equine Asthma: Current Understanding and Future Directions.. Front Vet Sci 2020;7:450.
- 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.
- 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.
- Davis KU, Sheats MK. Bronchoalveolar Lavage Cytology Characteristics and Seasonal Changes in a Herd of Pastured Teaching Horses.. Front Vet Sci 2019;6:74.
- Tessier L, Cu00f4tu00e9 O, Clark ME, Viel L, Diaz-Mu00e9ndez 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.
- Bond S, Lu00e9guillette 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.
- 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.
- Pacholewska A, Kraft MF, Gerber V, Jagannathan V. Differential Expression of Serum MicroRNAs Supports CD4u207a T Cell Differentiation into Th2/Th17 Cells in Severe Equine Asthma.. Genes (Basel) 2017 Dec 12;8(12).
- 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.
- Tessier L, Cu00f4tu00e9 O, Clark ME, Viel L, Diaz-Mu00e9ndez 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.
- 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.
- 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.