Analyze Diet
BMC veterinary research2008; 4; 8; doi: 10.1186/1746-6148-4-8

Epithelial expression of mRNA and protein for IL-6, IL-10 and TNF-alpha in endobronchial biopsies in horses with recurrent airway obstruction.

Abstract: The aim of this study was to evaluate the contribution of bronchial epithelium to airway inflammation, with focus on mRNA and protein expression of cytokines of innate immunity IL-6, IL-10 and TNF-alpha, in horses with Recurrent Airway Obstruction (RAO) during exacerbation and in remission. Results: Despite marked clinical and physiologic alterations between exacerbation and after remission in the RAO horses no differences were detected in either cytokine mRNA or protein levels. Moreover, the expression of investigated cytokines in RAO horses on pasture did not differ from controls. In comparing real-time PCR analysis to results of immunohistochemistry only IL-10 mRNA and protein levels in RAO horses on pasture were significantly correlated (rs = 0.893, p = 0.007). Curiously, in controls examined on pasture the TNF-alpha protein level was positively correlated to IL-10 mRNA expression (rs = 0.967, p = 0.007) and negatively correlated to IL-6 mRNA expression (rs = -0.971, p = 0.001). Conclusions: Given the complementary relationship of assessing cytokines directly by immunohistochemistry, or indirectly by PCR to mRNA, the lack of significant changes in either mRNA or protein levels of IL-6, IL-10 or TNF-alpha mRNA in RAO horses in exacerbation suggests that these particular cytokines in bronchial tissue may not play a substantive role in the active inflammation of this disease. To support this contention further studies examining time dependency of expression of IL-6, IL-10 or TNF-alpha are needed, as is expansion of the range of cytokines to include other key regulators of airway inflammation.
Publication Date: 2008-02-23 PubMed ID: 18294392PubMed Central: PMC2294109DOI: 10.1186/1746-6148-4-8Google 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 the role of specific cytokines in the bronchial inflammation associated with Recurrent Airway Obstruction (RAO) in horses. The results show that these cytokines may not play a significant role in active inflammation during RAO exacerbation.

Objective of the Study

  • The researchers aimed to analyze the role of bronchial epithelium in airway inflammation during RAO in horses. They focused specifically on mRNA and protein expression of immune system cytokines IL-6, IL-10 and TNF-alpha during both periods of disease exacerbation and remission.

Exacerbation and Remission of RAO in Horses

  • Despite noticing clinical and physiological changes between periods of RAO exacerbation and remission, the researchers found no differences in cytokine mRNA or protein levels in these horses.
  • It was also observed that the cytokine expression in RAO horses on pasture was similar to control horses not suffering from RAO.

Correlation Analysis

  • When comparing the results of cytokine analysis using real-time PCR (polymerase chain reaction) and immunohistochemistry, they found only one significant correlation in RAO horses on pasture. The IL-10 mRNA and protein levels showed a significant positive correlation.
  • In control horses on pasture, the protein level of TNF-alpha was found to be positively correlated to IL-10 mRNA expression, and negatively correlated to IL-6 mRNA expression.

Conclusions

  • The research suggests that the lack of substantial changes in mRNA or protein levels of IL-6, IL-10, or TNF-alpha in RAO horses during exacerbation implies that these specific cytokines may not play a significant role in inflammation associated with this disease.
  • To confirm this hypothesis, the researchers suggest further research is necessary to study the time-dependent expression of these cytokines, and possibly expanding the study to include other cytokines that may regulate airway inflammation.

Cite This Article

APA
Riihimäki M, Raine A, Pourazar J, Sandström T, Art T, Lekeux P, Couëtil L, Pringle J. (2008). Epithelial expression of mRNA and protein for IL-6, IL-10 and TNF-alpha in endobronchial biopsies in horses with recurrent airway obstruction. BMC Vet Res, 4, 8. https://doi.org/10.1186/1746-6148-4-8

Publication

ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 4
Pages: 8

Researcher Affiliations

Riihimäki, Miia
  • Department of Clinical Sciences, Equine Internal Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden. Miia.Riihimaki@kv.slu.se
Raine, Amanda
    Pourazar, Jamshid
      Sandström, Thomas
        Art, Tatiana
          Lekeux, Pierre
            Couëtil, Laurent
              Pringle, John

                MeSH Terms

                • Animals
                • Biopsy / veterinary
                • Bronchi / cytology
                • Bronchi / metabolism
                • Epithelial Cells / metabolism
                • Gene Expression Regulation
                • Horse Diseases / genetics
                • Horse Diseases / metabolism
                • Horses
                • Interleukin-1 / genetics
                • Interleukin-1 / metabolism
                • Interleukin-10 / genetics
                • Interleukin-10 / metabolism
                • Lung Diseases, Obstructive / genetics
                • Lung Diseases, Obstructive / metabolism
                • Lung Diseases, Obstructive / veterinary
                • RNA, Messenger / genetics
                • RNA, Messenger / metabolism
                • Respiratory Mucosa / cytology
                • Respiratory Mucosa / metabolism
                • Tumor Necrosis Factor-alpha / genetics
                • Tumor Necrosis Factor-alpha / metabolism

                References

                This article includes 32 references
                1. Knight DA, Holgate ST. The airway epithelium: structural and functional properties in health and disease.. Respirology 2003 Dec;8(4):432-46.
                2. Takizawa H. Bronchial epithelial cells in allergic reactions.. Curr Drug Targets Inflamm Allergy 2005 Jun;4(3):305-11.
                  doi: 10.2174/1568010054022123pubmed: 16101538google scholar: lookup
                3. Takizawa H. Airway epithelial cells as regulators of airway inflammation (Review).. Int J Mol Med 1998 Feb;1(2):367-78.
                  pubmed: 9852239doi: 10.3892/ijmm.1.2.367google scholar: lookup
                4. Holgate ST, Lackie P, Wilson S, Roche W, Davies D. Bronchial epithelium as a key regulator of airway allergen sensitization and remodeling in asthma.. Am J Respir Crit Care Med 2000 Sep;162(3 Pt 2):S113-7.
                5. Holgate ST. Inflammatory and structural changes in the airways of patients with asthma.. Respir Med 2000 Sep;94 Suppl D:S3-6.
                  pubmed: 11003167doi: 10.1016/s0954-6111(00)90116-1google scholar: lookup
                6. Pepe C, Foley S, Shannon J, Lemiere C, Olivenstein R, Ernst P, Ludwig MS, Martin JG, Hamid Q. Differences in airway remodeling between subjects with severe and moderate asthma.. J Allergy Clin Immunol 2005 Sep;116(3):544-9.
                  doi: 10.1016/j.jaci.2005.06.011pubmed: 16159622google scholar: lookup
                7. Brown JL, Behndig AF, Sekerel BE, Pourazar J, Blomberg A, Kelly FJ, Sandström T, Frew AJ, Wilson SJ. Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls.. Clin Exp Allergy 2007 May;37(5):688-95.
                8. Pourazar J, Mudway IS, Samet JM, Helleday R, Blomberg A, Wilson SJ, Frew AJ, Kelly FJ, Sandström T. Diesel exhaust activates redox-sensitive transcription factors and kinases in human airways.. Am J Physiol Lung Cell Mol Physiol 2005 Nov;289(5):L724-30.
                  doi: 10.1152/ajplung.00055.2005pubmed: 15749742google scholar: lookup
                9. Wallin A, Sue-Chu M, Bjermer L, Ward J, Sandström T, Lindberg A, Lundbäck B, Djukanović R, Holgate S, Wilson S. Effect of inhaled fluticasone with and without salmeterol on airway inflammation in asthma.. J Allergy Clin Immunol 2003 Jul;112(1):72-8.
                  doi: 10.1067/mai.2003.1518pubmed: 12847482google scholar: lookup
                10. Fabbri LM, Durham S, Holgate ST, O'Byrne PM, Postma DS. Assessment of airway inflammation: an overview.. Eur Respir J Suppl 1998 Mar;26:6S-8S.
                  pubmed: 9585871
                11. Jeffery P, Holgate S, Wenzel S. Methods for the assessment of endobronchial biopsies in clinical research: application to studies of pathogenesis and the effects of treatment.. Am J Respir Crit Care Med 2003 Sep 15;168(6 Pt 2):S1-17.
                  doi: 10.1164/rccm.200202-150WSpubmed: 14555461google scholar: lookup
                12. Howarth PH, Bradding P, Montefort S, Peroni D, Djukanovic R, Carroll MP, Holgate ST. Mucosal inflammation and asthma.. Am J Respir Crit Care Med 1994 Nov;150(5 Pt 2):S18-22.
                  pubmed: 7952584doi: 10.1164/ajrccm/150.5_Pt_2.S18google scholar: lookup
                13. Ainsworth DM, Grünig G, Matychak MB, Young J, Wagner B, Erb HN, Antczak DF. Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2003 Nov 15;96(1-2):83-91.
                  doi: 10.1016/S0165-2427(03)00142-9pubmed: 14522137google scholar: lookup
                14. Ainsworth DM, Wagner B, Franchini M, Grünig G, Erb HN, Tan JY. Time-dependent alterations in gene expression of interleukin-8 in the bronchial epithelium of horses with recurrent airway obstruction.. Am J Vet Res 2006 Apr;67(4):669-77.
                  doi: 10.2460/ajvr.67.4.669pubmed: 16579761google scholar: lookup
                15. Davis MS, Malayer JR, Vandeventer L, Royer CM, McKenzie EC, Williamson KK. Cold weather exercise and airway cytokine expression.. J Appl Physiol (1985) 2005 Jun;98(6):2132-6.
                16. Davis MS, Williams CC, Meinkoth JH, Malayer JR, Royer CM, Williamson KK, McKenzie EC. Influx of neutrophils and persistence of cytokine expression in airways of horses after performing exercise while breathing cold air.. Am J Vet Res 2007 Feb;68(2):185-9.
                  doi: 10.2460/ajvr.68.2.185pubmed: 17269885google scholar: lookup
                17. Berndt A, Derksen FJ, Venta PJ, Ewart S, Yuzbasiyan-Gurkan V, Robinson NE. Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction.. Am J Physiol Lung Cell Mol Physiol 2007 Apr;292(4):L936-43.
                  pubmed: 17158595doi: 10.1152/ajplung.00394.2006google scholar: lookup
                18. 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
                19. Gerber V, Robinson NE, Venta RJ, Rawson J, Jefcoat AM, Hotchkiss JA. Mucin genes in horse airways: MUC5AC, but not MUC2, may play a role in recurrent airway obstruction.. Equine Vet J 2003 May;35(3):252-7.
                  doi: 10.2746/042516403776148291pubmed: 12755427google scholar: lookup
                20. Laan TT, Bull S, Pirie R, Fink-Gremmels J. The role of alveolar macrophages in the pathogenesis of recurrent airway obstruction in horses.. J Vet Intern Med 2006 Jan-Feb;20(1):167-74.
                21. Giguère S, Viel L, Lee E, MacKay RJ, Hernandez J, Franchini M. Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.. Vet Immunol Immunopathol 2002 Mar;85(3-4):147-58.
                  doi: 10.1016/S0165-2427(01)00420-2pubmed: 11943316google scholar: lookup
                22. van den Hoven R, Duvigneau JC, Hartl RT, Gemeiner M. Clenbuterol affects the expression of messenger RNA for interleukin 10 in peripheral leukocytes from horses challenged intrabronchially with lipopolysaccharides.. Vet Res Commun 2006 Nov;30(8):921-8.
                  doi: 10.1007/s11259-006-3383-4pubmed: 17139543google scholar: lookup
                23. Wang Z, Malmberg P, Larsson P, Larsson BM, Larsson K. Time course of interleukin-6 and tumor necrosis factor-alpha increase in serum following inhalation of swine dust.. Am J Respir Crit Care Med 1996 Jan;153(1):147-52.
                  pubmed: 8542108doi: 10.1164/ajrccm.153.1.8542108google scholar: lookup
                24. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.. J Exp Med 1991 Nov 1;174(5):1209-20.
                  doi: 10.1084/jem.174.5.1209pmc: PMC2119001pubmed: 1940799google scholar: lookup
                25. Gamble E, Qiu Y, Wang D, Zhu J, Vignola AM, Kroegel C, Morell F, Hansel TT, Pavord ID, Rabe KF, Barnes NC, Jeffery PK. Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design.. Eur Respir J 2006 Feb;27(2):293-9.
                  doi: 10.1183/09031936.06.00027705pubmed: 16452583google scholar: lookup
                26. Haley KJ, Sunday ME, Wiggs BR, Kozakewich HP, Reilly JJ, Mentzer SJ, Sugarbaker DJ, Doerschuk CM, Drazen JM. Inflammatory cell distribution within and along asthmatic airways.. Am J Respir Crit Care Med 1998 Aug;158(2):565-72.
                  pubmed: 9700136doi: 10.1164/ajrccm.158.2.9705036google scholar: lookup
                27. Art T, Franck T, Lekeux P, de Moffarts B, Couëtil L, Becker M, Kohnen S, Deby-Dupont G, Serteyn D. Myeloperoxidase concentration in bronchoalveolar lavage fluid from healthy horses and those with recurrent airway obstruction.. Can J Vet Res 2006 Oct;70(4):291-6.
                  pmc: PMC1562538pubmed: 17042382
                28. Couëtil LL, Art T, de Moffarts B, Becker M, Mélotte D, Jaspar F, Bureau F, Lekeux P. DNA binding activity of transcription factors in bronchial cells of horses with recurrent airway obstruction.. Vet Immunol Immunopathol 2006 Sep 15;113(1-2):11-20.
                  doi: 10.1016/j.vetimm.2006.03.020pubmed: 16753225google scholar: lookup
                29. Riihimäki M, Raine A, Art T, Lekeux P, Couëtil L, Pringle J. Partial divergence of cytokine mRNA expression in bronchial tissues compared to bronchoalveolar lavage cells in horses with recurrent airway obstruction.. Vet Immunol Immunopathol 2008 Apr 15;122(3-4):256-64.
                  pubmed: 18243337doi: 10.1016/j.vetimm.2007.12.001google scholar: lookup
                30. You L, Yin J. Patterns of regulation from mRNA and protein time series.. Metab Eng 2000 Jul;2(3):210-7.
                  doi: 10.1006/mben.1999.0139pubmed: 11056063google scholar: lookup
                31. Britten KM, Howarth PH, Roche WR. Immunohistochemistry on resin sections: a comparison of resin embedding techniques for small mucosal biopsies.. Biotech Histochem 1993 Sep;68(5):271-80.
                  doi: 10.3109/10520299309105629pubmed: 8268322google scholar: lookup
                32. Couëtil LL, Art T, de Moffarts B, Becker M, Mélotte D, Jaspar F, Bureau F, Lekeux P. Effect of beclomethasone dipropionate and dexamethasone isonicotinate on lung function, bronchoalveolar lavage fluid cytology, and transcription factor expression in airways of horses with recurrent airway obstruction.. J Vet Intern Med 2006 Mar-Apr;20(2):399-406.

                Citations

                This article has been cited 7 times.
                1. Sheats MK, Davis KU, Poole JA. Comparative Review of Asthma in Farmers and Horses. Curr Allergy Asthma Rep 2019 Oct 10;19(11):50.
                  doi: 10.1007/s11882-019-0882-2pubmed: 31599358google scholar: lookup
                2. Barton AK, Pelli A, Rieger M, Gehlen H. Procalcitonin as a biomarker in equine chronic pneumopathies. BMC Vet Res 2016 Dec 9;12(1):281.
                  doi: 10.1186/s12917-016-0912-4pubmed: 27938364google scholar: lookup
                3. Bullone M, Hélie P, Joubert P, Lavoie JP. Development of a Semiquantitative Histological Score for the Diagnosis of Heaves Using Endobronchial Biopsy Specimens in Horses. J Vet Intern Med 2016 Sep;30(5):1739-1746.
                  doi: 10.1111/jvim.14556pubmed: 27527123google scholar: lookup
                4. Karagianni AE, Kapetanovic R, McGorum BC, Hume DA, Pirie SR. The equine alveolar macrophage: functional and phenotypic comparisons with peritoneal macrophages. Vet Immunol Immunopathol 2013 Oct 1;155(4):219-28.
                  doi: 10.1016/j.vetimm.2013.07.003pubmed: 23978307google scholar: lookup
                5. Beekman L, Tohver T, Dardari R, Léguillette R. Evaluation of suitable reference genes for gene expression studies in bronchoalveolar lavage cells from horses with inflammatory airway disease. BMC Mol Biol 2011 Jan 28;12:5.
                  doi: 10.1186/1471-2199-12-5pubmed: 21272375google scholar: lookup
                6. Pietra M, Morini M, Perfetti G, Spadari A, Vigo P, Peli A. Comparison of endoscopy, histology, and cytokine mRNA of the equine gastric mucosa. Vet Res Commun 2010 Jun;34 Suppl 1:S121-4.
                  doi: 10.1007/s11259-010-9401-6pubmed: 20473566google scholar: lookup
                7. Bueno VC, Bastos HBA, Centeno LA, Kretzmann NA, Mattos RC, Rechsteiner SF. PLCζ, WBP2NL and TNF-α expression in spermatozoa is associated with stallion fertility and seminal quality?. Anim Reprod 2024;21(1):e20230088.
                  doi: 10.1590/1984-3143-AR2023-0088pubmed: 38628496google scholar: lookup