Analyze Diet
BMC genomics2017; 18(1); 34; doi: 10.1186/s12864-016-3390-y

LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells.

Abstract: Lipopolysaccharide (endotoxin, LPS) is a strong inducer of the innate immune response. It is widespread in our environment, e.g. in house dust and contributes to asthma. Compared to humans, horses are even more sensitive to LPS. However, data on LPS effects on the equine transcriptome are very limited. Using RNA-seq we analysed LPS-induced differences in the gene expression in equine peripheral blood mononuclear cells at the gene and gene-network level in two half-sib families and one group of unrelated horses. 24 h-LPS challenge of equine immune cells resulted in substantial changes in the transcriptomic profile (1,265 differentially expressed genes) showing partial overlap with human data. One of the half-sib families showed a specific response different from the other two groups of horses. We also identified co-expressed gene modules that clearly differentiated 24 h-LPS- from non-stimulated samples. These modules consisted of 934 highly interconnected genes and included genes involved in the immune response (e.g. IL6, CCL22, CXCL6, CXCL2), however, none of the top ten hub genes of the modules have been annotated as responsive to LPS in gene ontology. Using weighted gene co-expression network analysis we identified ten co-expressed gene modules significantly regulated by in vitro stimulation with LPS. Apart from 47 genes (5%) all other genes highly interconnected within the most up- and down-regulated modules were also significantly differentially expressed (FDR < 0.05). The LPS-regulated module hub genes have not yet been described as having a role in the immune response to LPS (e.g. VAT1 and TTC25).
Publication Date: 2017-01-05 PubMed ID: 28056766PubMed Central: PMC5217269DOI: 10.1186/s12864-016-3390-yGoogle 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 research article investigates how lipopolysaccharide (LPS), a strong stimulator of the immune response, affects the gene expression in horses’ peripheral blood mononuclear cells. By analyzing RNA sequences, the researchers identified several gene co-expression networks significantly affected by LPS stimulation.

Study Background

  • The study revolves around Lipopolysaccharide (LPS), an endotoxin known to trigger the innate immune response. This substance is commonly found in environments such as house dust and thus has a significant impact on health conditions like asthma. The researchers noted that horses are even more sensitive to LPS in comparison to humans.
  • Despite this sensitivity, there is limited data on how LPS affects the equine (horses’) transcriptome – the complete set of transcripts in a cell, which offers more understanding of genetic activity.

Research Methodology and Results

  • The researchers used RNA sequencing to examine differences in gene expression induced by LPS in equine peripheral blood mononuclear cells. Consideration was given to both gene and network levels across two half-sib families and a group of unrelated horses.
  • Stimulation of equine immune cells with LPS for 24 hours resulted in significant changes to the transcriptomic profile, with 1,265 differentially expressed genes identified. Some of these changes were found to partially overlap with previous data on humans.
  • One of the half-sib families exhibited a distinct response compared to the other groups of horses studied.
  • The study also discovered co-expressed gene modules (sets of genes expressed together) differentiating LPS-stimulated samples from non-stimulated ones.

Co-expressed Gene Modules

  • The co-expressed gene modules consisted of 934 highly interconnected genes, including those involved in immune response (e.g., IL6, CCL22, CXCL6, CXCL2). However, none of the top ten hub genes in these modules were previously annotated as being responsive to LPS according to gene ontology.
  • Using weighted gene co-expression network analysis (a method for describing the correlation patterns among genes), the team uncovered ten co-expressed gene modules that were significantly regulated by in vitro (in a controlled lab setting) LPS stimulation.
  • 47 out of these genes were highly interconnected within the most upregulated and down-regulated modules, and they were also significantly differentially expressed. Conversely, the hub genes of the LPS-regulated modules (such as VAT1 and TTC25) have not been previously linked to immune response to LPS.

Cite This Article

APA
Pacholewska A, Marti E, Leeb T, Jagannathan V, Gerber V. (2017). LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells. BMC Genomics, 18(1), 34. https://doi.org/10.1186/s12864-016-3390-y

Publication

ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 18
Issue: 1
Pages: 34
PII: 34

Researcher Affiliations

Pacholewska, Alicja
  • Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Länggassstrasse 124, 3012, Bern, Switzerland. alicja@rth.dk.
  • Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012, Bern, Switzerland. alicja@rth.dk.
Marti, Eliane
  • Department of Clinical Research and Veterinary Public Health, Division of Experimental Clinical Research, Vetsuisse Faculty, University of Bern, Länggassstrasse 124, 3012, Bern, Switzerland.
Leeb, Tosso
  • Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012, Bern, Switzerland.
Jagannathan, Vidhya
  • Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012, Bern, Switzerland.
Gerber, Vincent
  • Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Länggassstrasse 124, 3012, Bern, Switzerland.

MeSH Terms

  • Animals
  • Cluster Analysis
  • Computational Biology / methods
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks
  • Genetic Background
  • Horses
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides / immunology
  • Transcriptome

References

This article includes 106 references
  1. Janeway CA Jr. Approaching the asymptote? Evolution and revolution in immunology.. Cold Spring Harb Symp Quant Biol 1989;54 Pt 1:1-13.
    doi: 10.1101/SQB.1989.054.01.003pubmed: 2700931google scholar: lookup
  2. OSBORN MJ, ROSEN SM, ROTHFIELD L, ZELEZNICK LD, HORECKER BL. LIPOPOLYSACCHARIDE OF THE GRAM-NEGATIVE CELL WALL.. Science 1964 Aug 21;145(3634):783-9.
    doi: 10.1126/science.145.3634.783pubmed: 14163315google scholar: lookup
  3. Schütt C. Fighting infection: the role of lipopolysaccharide binding proteins CD14 and LBP.. Pathobiology 1999;67(5-6):227-9.
    doi: 10.1159/000028097pubmed: 10725789google scholar: lookup
  4. Tobias PS, Soldau K, Ulevitch RJ. Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum.. J Exp Med 1986 Sep 1;164(3):777-93.
    doi: 10.1084/jem.164.3.777pmc: PMC2188379pubmed: 2427635google scholar: lookup
  5. Janeway CA Jr, Medzhitov R. Innate immune recognition.. Annu Rev Immunol 2002;20:197-216.
  6. Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response.. Nature 2000 Aug 17;406(6797):782-7.
    doi: 10.1038/35021228pubmed: 10963608google scholar: lookup
  7. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.. Nat Immunol 2010 May;11(5):373-84.
    doi: 10.1038/ni.1863pubmed: 20404851google scholar: lookup
  8. Akira S, Hemmi H. Recognition of pathogen-associated molecular patterns by TLR family.. Immunol Lett 2003 Jan 22;85(2):85-95.
    doi: 10.1016/S0165-2478(02)00228-6pubmed: 12527213google scholar: lookup
  9. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.. Nature 1997 Jul 24;388(6640):394-7.
    doi: 10.1038/41131pubmed: 9237759google scholar: lookup
  10. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses.. Clin Microbiol Rev 2009 Apr;22(2):240-73, Table of Contents.
    doi: 10.1128/CMR.00046-08pmc: PMC2668232pubmed: 19366914google scholar: lookup
  11. Buras JA, Holzmann B, Sitkovsky M. Animal models of sepsis: setting the stage.. Nat Rev Drug Discov 2005 Oct;4(10):854-65.
    doi: 10.1038/nrd1854pubmed: 16224456google scholar: lookup
  12. Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS.. Crit Care Med 1996 Jul;24(7):1125-8.
  13. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000.. N Engl J Med 2003 Apr 17;348(16):1546-54.
    doi: 10.1056/NEJMoa022139pubmed: 12700374google scholar: lookup
  14. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine.. Chest 1992 Jun;101(6):1644-55.
    doi: 10.1378/chest.101.6.1644pubmed: 1303622google scholar: lookup
  15. Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.. Pediatr Crit Care Med 2005 Jan;6(1):2-8.
  16. Ulloa L, Tracey KJ. The "cytokine profile": a code for sepsis.. Trends Mol Med 2005 Feb;11(2):56-63.
    doi: 10.1016/j.molmed.2004.12.007pubmed: 15694867google scholar: lookup
  17. Liu AH. Endotoxin exposure in allergy and asthma: reconciling a paradox.. J Allergy Clin Immunol 2002 Mar;109(3):379-92.
    doi: 10.1067/mai.2002.122157pubmed: 11897980google scholar: lookup
  18. Michel O. Systemic and local airways inflammatory response to endotoxin.. Toxicology 2000 Nov 2;152(1-3):25-30.
    doi: 10.1016/S0300-483X(00)00288-2pubmed: 11090936google scholar: lookup
  19. Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans.. Nat Genet 2000 Jun;25(2):187-91.
    doi: 10.1038/76048pubmed: 10835634google scholar: lookup
  20. Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K. Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen.. J Exp Med 2002 Dec 16;196(12):1645-51.
    doi: 10.1084/jem.20021340pmc: PMC2196061pubmed: 12486107google scholar: lookup
  21. Braun-Fahrländer C, Riedler J, Herz U, Eder W, Waser M, Grize L, Maisch S, Carr D, Gerlach F, Bufe A, Lauener RP, Schierl R, Renz H, Nowak D, von Mutius E. Environmental exposure to endotoxin and its relation to asthma in school-age children.. N Engl J Med 2002 Sep 19;347(12):869-77.
    doi: 10.1056/NEJMoa020057pubmed: 12239255google scholar: lookup
  22. Tulić MK, Wale JL, Holt PG, Sly PD. Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide.. Am J Respir Cell Mol Biol 2000 May;22(5):604-12.
    doi: 10.1165/ajrcmb.22.5.3710pubmed: 10783133google scholar: lookup
  23. Reed CE, Milton DK. Endotoxin-stimulated innate immunity: A contributing factor for asthma.. J Allergy Clin Immunol 2001 Aug;108(2):157-66.
    doi: 10.1067/mai.2001.116862pubmed: 11496229google scholar: lookup
  24. Yazdani N, Amoli MM, Naraghi M, Mersaghian A, Firouzi F, Sayyahpour F, Mokhtari Z. Association between the functional polymorphism C-159T in the CD14 promoter gene and nasal polyposis: potential role in asthma.. J Investig Allergol Clin Immunol 2012;22(6):406-11.
    pubmed: 23101184
  25. Baldini M, Lohman IC, Halonen M, Erickson RP, Holt PG, Martinez FD. A Polymorphism* in the 5' flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E.. Am J Respir Cell Mol Biol 1999 May;20(5):976-83.
    doi: 10.1165/ajrcmb.20.5.3494pubmed: 10226067google scholar: lookup
  26. Sackesen C, Birben E, Soyer OU, Sahiner UM, Yavuz TS, Civelek E, Karabulut E, Akdis M, Akdis CA, Kalayci O. The effect of CD14 C159T polymorphism on in vitro IgE synthesis and cytokine production by PBMC from children with asthma.. Allergy 2011 Jan;66(1):48-57.
  27. Singh Suri S, Janardhan KS, Parbhakar O, Caldwell S, Appleyard G, Singh B. Expression of toll-like receptor 4 and 2 in horse lungs.. Vet Res 2006 Jul-Aug;37(4):541-51.
    doi: 10.1051/vetres:2006017pubmed: 16641015google scholar: lookup
  28. Warren HS. Editorial: Mouse models to study sepsis syndrome in humans.. J Leukoc Biol 2009 Aug;86(2):199-201.
    doi: 10.1189/jlb.0309210pubmed: 19643738google scholar: lookup
  29. Werners AH, Bull S, Fink-Gremmels J. Endotoxaemia: a review with implications for the horse.. Equine Vet J 2005 Jul;37(4):371-83.
    doi: 10.2746/0425164054529418pubmed: 16028631google scholar: lookup
  30. Sykes BW, Furr MO. Equine endotoxaemia--a state-of-the-art review of therapy.. Aust Vet J 2005 Jan-Feb;83(1-2):45-50.
  31. Senior JM, Proudman CJ, Leuwer M, Carter SD. Plasma endotoxin in horses presented to an equine referral hospital: correlation to selected clinical parameters and outcomes.. Equine Vet J 2011 Sep;43(5):585-91.
  32. 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.
  33. 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
  34. 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
  35. 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.
  36. Gerber V, Tessier C, Marti E. Genetics of upper and lower airway diseases in the horse.. Equine Vet J 2015 Jul;47(4):390-7.
    pubmed: 24773614doi: 10.1111/evj.12289google scholar: lookup
  37. 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.
  38. 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.
  39. Pirie RS, Dixon PM, Collie DD, McGorum BC. Pulmonary and systemic effects of inhaled endotoxin in control and heaves horses.. Equine Vet J 2001 May;33(3):311-8.
    doi: 10.2746/042516401776249732pubmed: 11352355google scholar: lookup
  40. 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.
  41. Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells.. Nat Med 2009 Apr;15(4):410-6.
    doi: 10.1038/nm.1946pmc: PMC2789255pubmed: 19330007google scholar: lookup
  42. Nowak MA, Boerlijst MC, Cooke J, Smith JM. Evolution of genetic redundancy.. Nature 1997 Jul 10;388(6638):167-71.
    doi: 10.1038/40618pubmed: 9217155google scholar: lookup
  43. Stuart JM, Segal E, Koller D, Kim SK. A gene-coexpression network for global discovery of conserved genetic modules.. Science 2003 Oct 10;302(5643):249-55.
    doi: 10.1126/science.1087447pubmed: 12934013google scholar: lookup
  44. Aggarwal A, Guo DL, Hoshida Y, Yuen ST, Chu KM, So S, Boussioutas A, Chen X, Bowtell D, Aburatani H, Leung SY, Tan P. Topological and functional discovery in a gene coexpression meta-network of gastric cancer.. Cancer Res 2006 Jan 1;66(1):232-41.
    doi: 10.1158/0008-5472.CAN-05-2232pubmed: 16397236google scholar: lookup
  45. Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns.. Proc Natl Acad Sci U S A 1998 Dec 8;95(25):14863-8.
    doi: 10.1073/pnas.95.25.14863pmc: PMC24541pubmed: 9843981google scholar: lookup
  46. Cookson W, Liang L, Abecasis G, Moffatt M, Lathrop M. Mapping complex disease traits with global gene expression.. Nat Rev Genet 2009 Mar;10(3):184-94.
    doi: 10.1038/nrg2537pmc: PMC4550035pubmed: 19223927google scholar: lookup
  47. Luo F, Yang Y, Zhong J, Gao H, Khan L, Thompson DK, Zhou J. Constructing gene co-expression networks and predicting functions of unknown genes by random matrix theory.. BMC Bioinformatics 2007 Aug 14;8:299.
    pmc: PMC2212665pubmed: 17697349doi: 10.1186/1471-2105-8-299google scholar: lookup
  48. Crowther D, Fairley GH, Sewell RL. Lymphoid cellular responses in the blood after immunization in man.. J Exp Med 1969 May 1;129(5):849-69.
    doi: 10.1084/jem.129.5.849pmc: PMC2138644pubmed: 5778787google scholar: lookup
  49. 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
  50. Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.. PLoS One 2015;10(8):e0136103.
  51. Ernst M, Kern P, Flad HD, Ulmer AJ. Effects of systemic in vivo interleukin-2 (IL-2) reconstitution in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) on phenotypes and functions of peripheral blood mononuclear cells (PBMC).. J Clin Immunol 1986 Mar;6(2):170-81.
    pubmed: 2940258doi: 10.1007/bf00918750google scholar: lookup
  52. Moreno J, Nieto J, Chamizo C, González F, Blanco F, Barker DC, Alvar J. The immune response and PBMC subsets in canine visceral leishmaniasis before, and after, chemotherapy.. Vet Immunol Immunopathol 1999 Nov 30;71(3-4):181-95.
    doi: 10.1016/S0165-2427(99)00096-3pubmed: 10587300google scholar: lookup
  53. Kierstead LS, Dubey S, Meyer B, Tobery TW, Mogg R, Fernandez VR, Long R, Guan L, Gaunt C, Collins K, Sykes KJ, Mehrotra DV, Chirmule N, Shiver JW, Casimiro DR. Enhanced rates and magnitude of immune responses detected against an HIV vaccine: effect of using an optimized process for isolating PBMC.. AIDS Res Hum Retroviruses 2007 Jan;23(1):86-92.
    doi: 10.1089/aid.2006.0129pubmed: 17263637google scholar: lookup
  54. Hutchins WA, Kieber-Emmons T, Carlone GM, Westerink MA. Human immune response to a peptide mimic of Neisseria meningitidis serogroup C in hu-PBMC-SCID mice.. Hybridoma 1999 Apr;18(2):121-9.
    doi: 10.1089/hyb.1999.18.121pubmed: 10380011google scholar: lookup
  55. Meade KG, Gormley E, Park SD, Fitzsimons T, Rosa GJ, Costello E, Keane J, Coussens PM, MacHugh DE. Gene expression profiling of peripheral blood mononuclear cells (PBMC) from Mycobacterium bovis infected cattle after in vitro antigenic stimulation with purified protein derivative of tuberculin (PPD).. Vet Immunol Immunopathol 2006 Sep 15;113(1-2):73-89.
    doi: 10.1016/j.vetimm.2006.04.012pubmed: 16784781google scholar: lookup
  56. 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.
  57. 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.
  58. 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.
  59. Huber W, von Heydebreck A, Sültmann H, Poustka A, Vingron M. Variance stabilization applied to microarray data calibration and to the quantification of differential expression.. Bioinformatics 2002;18 Suppl 1:S96-104.
  60. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK. limma powers differential expression analyses for RNA-sequencing and microarray studies.. Nucleic Acids Res 2015 Apr 20;43(7):e47.
    doi: 10.1093/nar/gkv007pmc: PMC4402510pubmed: 25605792google scholar: lookup
  61. Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc Ser B 1995;57:289–300.
  62. Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C, Arts P, Verwiel ET, Gresnigt MS, Fransen K, van Sommeren S, Oosting M, Cheng SC, Joosten LA, Hoischen A, Kullberg BJ, Scott WK, Perfect JR, van der Meer JW, Wijmenga C, Netea MG, Xavier RJ. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans.. Nat Commun 2013;4:1342.
    doi: 10.1038/ncomms2343pmc: PMC3625375pubmed: 23299892google scholar: lookup
  63. Metcalf TU, Cubas RA, Ghneim K, Cartwright MJ, Grevenynghe JV, Richner JM, Olagnier DP, Wilkinson PA, Cameron MJ, Park BS, Hiscott JB, Diamond MS, Wertheimer AM, Nikolich-Zugich J, Haddad EK. Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors.. Aging Cell 2015 Jun;14(3):421-32.
    doi: 10.1111/acel.12320pmc: PMC4406671pubmed: 25728020google scholar: lookup
  64. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva A. NCBI GEO: archive for functional genomics data sets--update.. Nucleic Acids Res 2013 Jan;41(Database issue):D991-5.
    pmc: PMC3531084pubmed: 23193258doi: 10.1093/nar/gks1193google scholar: lookup
  65. Mi H, Poudel S, Muruganujan A, Casagrande JT, Thomas PD. PANTHER version 10: expanded protein families and functions, and analysis tools.. Nucleic Acids Res 2016 Jan 4;44(D1):D336-42.
    doi: 10.1093/nar/gkv1194pmc: PMC4702852pubmed: 26578592google scholar: lookup
  66. Mi H, Muruganujan A, Casagrande JT, Thomas PD. Large-scale gene function analysis with the PANTHER classification system.. Nat Protoc 2013 Aug;8(8):1551-66.
    doi: 10.1038/nprot.2013.092pmc: PMC6519453pubmed: 23868073google scholar: lookup
  67. . The Gene Ontology's Reference Genome Project: a unified framework for functional annotation across species.. PLoS Comput Biol 2009 Jul;5(7):e1000431.
  68. 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: 10.1038/75556pmc: PMC3037419pubmed: 10802651google scholar: lookup
  69. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis.. BMC Bioinformatics 2008 Dec 29;9:559.
    doi: 10.1186/1471-2105-9-559pmc: PMC2631488pubmed: 19114008google scholar: lookup
  70. Suzuki T, Hashimoto S, Toyoda N, Nagai S, Yamazaki N, Dong HY, Sakai J, Yamashita T, Nukiwa T, Matsushima K. Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE.. Blood 2000 Oct 1;96(7):2584-91.
    pubmed: 11001915
  71. Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, Chen RO, Brownstein BH, Cobb JP, Tschoeke SK, Miller-Graziano C, Moldawer LL, Mindrinos MN, Davis RW, Tompkins RG, Lowry SF. A network-based analysis of systemic inflammation in humans.. Nature 2005 Oct 13;437(7061):1032-7.
    doi: 10.1038/nature03985pubmed: 16136080google scholar: lookup
  72. Cobb JP, Moore EE, Hayden DL, Minei JP, Cuschieri J, Yang J, Li Q, Lin N, Brownstein BH, Hennessy L, Mason PH, Schierding WS, Dixon DJ, Tompkins RG, Warren HS, Schoenfeld DA, Maier RV. Validation of the riboleukogram to detect ventilator-associated pneumonia after severe injury.. Ann Surg 2009 Oct;250(4):531-9.
  73. Wong HR, Shanley TP, Sakthivel B, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Doctor A, Kalyanaraman M, Tofil NM, Penfil S, Monaco M, Tagavilla MA, Odoms K, Dunsmore K, Barnes M, Aronow BJ. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome.. Physiol Genomics 2007 Jul 18;30(2):146-55.
  74. Scicluna BP, van 't Veer C, Nieuwdorp M, Felsmann K, Wlotzka B, Stroes ES, van der Poll T. Role of tumor necrosis factor-α in the human systemic endotoxin-induced transcriptome.. PLoS One 2013;8(11):e79051.
  75. 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.
    pmc: PMC4218705pubmed: 25371755doi: 10.3892/etm.2014.2025google scholar: lookup
  76. Wuyts A, Struyf S, Gijsbers K, Schutyser E, Put W, Conings R, Lenaerts JP, Geboes K, Opdenakker G, Menten P, Proost P, Van Damme J. The CXC chemokine GCP-2/CXCL6 is predominantly induced in mesenchymal cells by interleukin-1beta and is down-regulated by interferon-gamma: comparison with interleukin-8/CXCL8.. Lab Invest 2003 Jan;83(1):23-34.
  77. Scicluna BP, van der Poll T. Interleukin-27: a potential new sepsis biomarker exposed through genome-wide transcriptional profiling.. Crit Care 2012 Dec 27;16(6):188.
    doi: 10.1186/cc11893pmc: PMC3672618pubmed: 23270567google scholar: lookup
  78. Wong HR, Cvijanovich NZ, Hall M, Allen GL, Thomas NJ, Freishtat RJ, Anas N, Meyer K, Checchia PA, Lin R, Bigham MT, Sen A, Nowak J, Quasney M, Henricksen JW, Chopra A, Banschbach S, Beckman E, Harmon K, Lahni P, Shanley TP. Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children.. Crit Care 2012 Oct 29;16(5):R213.
    pmc: PMC3682317pubmed: 23107287doi: 10.1186/cc11847google scholar: lookup
  79. Muenzer JT, Davis CG, Chang K, Schmidt RE, Dunne WM, Coopersmith CM, Hotchkiss RS. Characterization and modulation of the immunosuppressive phase of sepsis.. Infect Immun 2010 Apr;78(4):1582-92.
    doi: 10.1128/IAI.01213-09pmc: PMC2849407pubmed: 20100863google scholar: lookup
  80. Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction.. Crit Care Med 1999 Jul;27(7):1230-51.
  81. Hotchkiss RS, Opal S. Immunotherapy for sepsis--a new approach against an ancient foe.. N Engl J Med 2010 Jul 1;363(1):87-9.
    doi: 10.1056/NEJMcibr1004371pmc: PMC4136660pubmed: 20592301google scholar: lookup
  82. Otto GP, Sossdorf M, Claus RA, Rödel J, Menge K, Reinhart K, Bauer M, Riedemann NC. The late phase of sepsis is characterized by an increased microbiological burden and death rate.. Crit Care 2011 Jul 28;15(4):R183.
    pmc: PMC3387626pubmed: 21798063doi: 10.1186/cc10332google scholar: lookup
  83. Hotchkiss RS, Osmon SB, Chang KC, Wagner TH, Coopersmith CM, Karl IE. Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways.. J Immunol 2005 Apr 15;174(8):5110-8.
    doi: 10.4049/jimmunol.174.8.5110pubmed: 15814742google scholar: lookup
  84. Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis.. Nat Rev Immunol 2006 Nov;6(11):813-22.
    doi: 10.1038/nri1943pubmed: 17039247google scholar: lookup
  85. Fernández M, Sánchez-Franco F, Palacios N, Sánchez I, Fernández C, Cacicedo L. IGF-I inhibits apoptosis through the activation of the phosphatidylinositol 3-kinase/Akt pathway in pituitary cells.. J Mol Endocrinol 2004 Aug;33(1):155-63.
    doi: 10.1677/jme.0.0330155pubmed: 15291750google scholar: lookup
  86. Castrillo A, Bodelón OG, Boscá L. Inhibitory effect of IGF-I on type 2 nitric oxide synthase expression in Ins-1 cells and protection against activation-dependent apoptosis: involvement of phosphatidylinositol 3-kinase.. Diabetes 2000 Feb;49(2):209-17.
    doi: 10.2337/diabetes.49.2.209pubmed: 10868937google scholar: lookup
  87. Willaime-Morawek S, Arbez N, Mariani J, Brugg B. IGF-I protects cortical neurons against ceramide-induced apoptosis via activation of the PI-3K/Akt and ERK pathways; is this protection independent of CREB and Bcl-2?. Brain Res Mol Brain Res 2005 Dec 14;142(2):97-106.
  88. Kooijman R. Regulation of apoptosis by insulin-like growth factor (IGF)-I.. Cytokine Growth Factor Rev 2006 Aug;17(4):305-23.
    doi: 10.1016/j.cytogfr.2006.02.002pubmed: 16621671google scholar: lookup
  89. Suh HS, Zhao ML, Derico L, Choi N, Lee SC. Insulin-like growth factor 1 and 2 (IGF1, IGF2) expression in human microglia: differential regulation by inflammatory mediators.. J Neuroinflammation 2013 Mar 12;10:37.
    doi: 10.1186/1742-2094-10-37pmc: PMC3607995pubmed: 23497056google scholar: lookup
  90. 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.
  91. Nussbaumer Schleuniger P, Frey CF, Gottstein B, Swinburne JE, Dolf G, Gerber V. Resistance against strongylid nematodes in two high prevalence Equine Recurrent Airway Obstruction families has a genetic basis. Pferdeheilkunde 2011;27:664–9.
    doi: 10.21836/PEM20110613google scholar: lookup
  92. Jin J, Xiao Y, Hu H, Zou Q, Li Y, Gao Y, Ge W, Cheng X, Sun SC. Proinflammatory TLR signalling is regulated by a TRAF2-dependent proteolysis mechanism in macrophages.. Nat Commun 2015 Jan 7;6:5930.
    doi: 10.1038/ncomms6930pmc: PMC4286812pubmed: 25565375google scholar: lookup
  93. Karjalainen M, Rintanen N, Lehkonen M, Kallio K, Mäki A, Hellström K, Siljamäki V, Upla P, Marjomäki V. Echovirus 1 infection depends on biogenesis of novel multivesicular bodies.. Cell Microbiol 2011 Dec;13(12):1975-95.
  94. Leung TH, Ching YP, Yam JW, Wong CM, Yau TO, Jin DY, Ng IO. Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity.. Proc Natl Acad Sci U S A 2005 Oct 18;102(42):15207-12.
    doi: 10.1073/pnas.0504501102pmc: PMC1250229pubmed: 16217026google scholar: lookup
  95. Faugaret D, Chouinard FC, Harbour D, El azreq MA, Bourgoin SG. An essential role for phospholipase D in the recruitment of vesicle amine transport protein-1 to membranes in human neutrophils.. Biochem Pharmacol 2011 Jan 1;81(1):144-56.
    doi: 10.1016/j.bcp.2010.09.014pubmed: 20858461google scholar: lookup
  96. Panaro MA, Mitolo V. Cellular responses to FMLP challenging: a mini-review.. Immunopharmacol Immunotoxicol 1999 Aug;21(3):397-419.
    doi: 10.3109/08923979909007117pubmed: 10466071google scholar: lookup
  97. Alcaide P, Merinero B, Ruiz-Sala P, Richard E, Navarrete R, Arias A, Ribes A, Artuch R, Campistol J, Ugarte M, Rodríguez-Pombo P. Defining the pathogenicity of creatine deficiency syndrome.. Hum Mutat 2011 Mar;32(3):282-91.
    doi: 10.1002/humu.21421pubmed: 21140503google scholar: lookup
  98. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells.. Nature 1997 Nov 27;390(6658):350-1.
    doi: 10.1038/37022pubmed: 9389474google scholar: lookup
  99. Patterson AM, Gardner L, Shaw J, David G, Loreau E, Aguilar L, Ashton BA, Middleton J. Induction of a CXCL8 binding site on endothelial syndecan-3 in rheumatoid synovium.. Arthritis Rheum 2005 Aug;52(8):2331-42.
    doi: 10.1002/art.21222pubmed: 16052590google scholar: lookup
  100. Sun YX, Tsuboi K, Zhao LY, Okamoto Y, Lambert DM, Ueda N. Involvement of N-acylethanolamine-hydrolyzing acid amidase in the degradation of anandamide and other N-acylethanolamines in macrophages.. Biochim Biophys Acta 2005 Oct 1;1736(3):211-20.
    pubmed: 16154384doi: 10.1016/j.bbalip.2005.08.010google scholar: lookup
  101. Solorzano C, Zhu C, Battista N, Astarita G, Lodola A, Rivara S, Mor M, Russo R, Maccarrone M, Antonietti F, Duranti A, Tontini A, Cuzzocrea S, Tarzia G, Piomelli D. Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation.. Proc Natl Acad Sci U S A 2009 Dec 8;106(49):20966-71.
    doi: 10.1073/pnas.0907417106pmc: PMC2791595pubmed: 19926854google scholar: lookup
  102. Li Y, Yang L, Chen L, Zhu C, Huang R, Zheng X, Qiu Y, Fu J. Design and synthesis of potent N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitor as anti-inflammatory compounds.. PLoS One 2012;7(8):e43023.
  103. Bandiera T, Ponzano S, Piomelli D. Advances in the discovery of N-acylethanolamine acid amidase inhibitors.. Pharmacol Res 2014 Aug;86:11-7.
    doi: 10.1016/j.phrs.2014.04.011pmc: PMC4117721pubmed: 24798679google scholar: lookup
  104. Fiasella A, Nuzzi A, Summa M, Armirotti A, Tarozzo G, Tarzia G, Mor M, Bertozzi F, Bandiera T, Piomelli D. 3-Aminoazetidin-2-one derivatives as N-acylethanolamine acid amidase (NAAA) inhibitors suitable for systemic administration.. ChemMedChem 2014 Jul;9(7):1602-14.
    doi: 10.1002/cmdc.201300546pmc: PMC4224963pubmed: 24828120google scholar: lookup
  105. Kuo TT, Baker K, Yoshida M, Qiao SW, Aveson VG, Lencer WI, Blumberg RS. Neonatal Fc receptor: from immunity to therapeutics.. J Clin Immunol 2010 Nov;30(6):777-89.
    doi: 10.1007/s10875-010-9468-4pmc: PMC2970823pubmed: 20886282google scholar: lookup
  106. Wallmeier J, Shiratori H, Dougherty GW, Edelbusch C, Hjeij R, Loges NT, Menchen T, Olbrich H, Pennekamp P, Raidt J, Werner C, Minegishi K, Shinohara K, Asai Y, Takaoka K, Lee C, Griese M, Memari Y, Durbin R, Kolb-Kokocinski A, Sauer S, Wallingford JB, Hamada H, Omran H. TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization.. Am J Hum Genet 2016 Aug 4;99(2):460-9.
    doi: 10.1016/j.ajhg.2016.06.014pmc: PMC4974089pubmed: 27486780google scholar: lookup

Citations

This article has been cited 7 times.
  1. Zapata-García JA, Riveros-Magaña AR, Ortiz-Lazareno PC, Hernández-Flores G, Jave-Suárez LF, Aguilar-Lemarroy A. Comparative Genomic Hybridization and Transcriptome Sequencing Reveal Genes with Gain in Acute Lymphoblastic Leukemia: JUP Expression Emerges as a Survival-Related Gene.. Diagnostics (Basel) 2022 Nov 14;12(11).
    doi: 10.3390/diagnostics12112788pubmed: 36428851google scholar: lookup
  2. Liu M, Yang P, Fu D, Gao T, Deng X, Shao M, Liao J, Jiang H, Li X. Allicin protects against myocardial I/R by accelerating angiogenesis via the miR-19a-3p/PI3K/AKT axis.. Aging (Albany NY) 2021 Oct 4;13(19):22843-22855.
    doi: 10.18632/aging.203578pubmed: 34607973google scholar: lookup
  3. Lorenz L, Hirmer S, Schmalen A, Hauck SM, Deeg CA. Cell Surface Profiling of Retinal Müller Glial Cells Reveals Association to Immune Pathways after LPS Stimulation.. Cells 2021 Mar 23;10(3).
    doi: 10.3390/cells10030711pubmed: 33806940google scholar: lookup
  4. Sheats MK. A Comparative Review of Equine SIRS, Sepsis, and Neutrophils.. Front Vet Sci 2019;6:69.
    doi: 10.3389/fvets.2019.00069pubmed: 30931316google scholar: lookup
  5. Tallmadge RL, Wang M, Sun Q, Felippe MJB. Transcriptome analysis of immune genes in peripheral blood mononuclear cells of young foals and adult horses.. PLoS One 2018;13(9):e0202646.
    doi: 10.1371/journal.pone.0202646pubmed: 30183726google scholar: lookup
  6. Sun M, Sun T, He Z, Xiong B. Identification of two novel biomarkers of rectal carcinoma progression and prognosis via co-expression network analysis.. Oncotarget 2017 Sep 19;8(41):69594-69609.
    doi: 10.18632/oncotarget.18646pubmed: 29050227google scholar: lookup
  7. Parkinson NJ, Buechner-Maxwell VA, Witonsky SG, Pleasant RS, Werre SR, Ahmed SA. Characterization of basal and lipopolysaccharide-induced microRNA expression in equine peripheral blood mononuclear cells using Next-Generation Sequencing.. PLoS One 2017;12(5):e0177664.
    doi: 10.1371/journal.pone.0177664pubmed: 28552958google scholar: lookup