Tracheal overexpression of IL-1β, IRAK-1 and TRAF-6 mRNA in obese-asthmatic male Wistar rats

Document Type : Original Article

Authors

1 Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

3 School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Objective(s): Human and animal studies have shown a close relationship between obesity and asthma severity. Here, we examined the effects of diet-induced obesity (DIO) on the expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA in male Wistar rats tracheal after sensitization with ovalbumin (OVA).
Materials and Methods:Twenty male Wistar rats divided to four groups, included, control group with normal diet (C+ND), OVA-sensitized group with normal diet (S+ND), control group with high-fat diet (C+HFD), and OVA-sensitized group with high-fat diet (S+HFD). All animals fed for 8 weeks with standard pelts or high-fat diet, and then were sensitized and challenged with OVA or saline for another 4 weeks with designed regimens. At the end of study, trachea isolated and examined for expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA with RT-PCR method.
Results:Diet-induced obesity groups developed increased weight, obesity indexes and lipid profiles (P<0.05 to P<0.001). The expression levels of IL-1β mRNA in OVA-sensitization groups (S+ND and S+HFD) showed a significantly increased when compared with control group. Also in S+HFD group, expression level of TRAF-6 mRNA was higher than other groups (P<0.001). IRAK-1 expression level was high in S+HFD compared with control group.IL-1β and TRAF-6 mRNA correlated positively with obesity indexes.
Conclusion:The results showed that DIO causes overexpression of IL-1β, IRAK-1 and TRAF-6 mRNA in an experimental model of asthma. Our results suggested that in obese-asthmatic conditions locally production and activation of pro-inflammatory agents can be increased. These findings showed that possible mechanism for obesity-asthma relationships.

Keywords

References

1.Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med 2007;175:661-666.
2.Thomson CC, Clark S, Camargo CA. Body mass index and asthma severity among adults presenting to the emergency department. CHEST 2003;124:795-802.
3.Lugogo NL, Kraft M, Dixon AE. Does obesity produce a distinct asthma phenotype? J Appl Physiol 2010;108:729-734.
4.Johnston RA, Theman TA, Lu FL, Terry RD, Williams ES, Shore SA. Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and enhances ozone-induced pulmonary inflammation. J Appl Physiol 2008;104:1727-1735.
5.Scherer PE. Adipose tissue from lipid storage compartment to endocrine organ. Diabetes 2006;55:1537-1545.
6.Shore SA, Fredberg JJ. Obesity, smooth muscle, and airway hyperresponsiveness. J Allergy Clin Immunol 2005;115:925-927.
7.Beuther DA. Recent insight into obesity and asthma. Curr Opin Pulm Med 2010;16:64-70.
8.Krause K, Metz M, Makris M, Zuberbier T, Maurer M. The role of interleukin-1 in allergy-related disorders. Curr Opin Allergy Clin Immunol 2012;12:477-484.
9.Hakonarson H, Grunstein MM. Autocrine regulation of airway smooth muscle responsiveness. Respir Physiol Neurobiol 2003;137:263-276.
10.Martin M, Resch K. Interleukin 1: more than a mediator between leukocytes. Trends Pharmacol Sci 1988;9:171-177.
11.Mantovani A, Dejana E. Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today 1989;10:370-375.
12.Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 2008;118:3546.
13.Selig W, Tocker J. Effect of interleukin-1 receptor antagonist on antigen-induced pulmonary responses in guinea pigs. Eur J Pharmacol 1992;213:331-336.
14.Dinarello CA. Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int Rev Immunol 1998;16:457-499.
15.Borish L, Mascali JJ, Dishuck J, Beam WR, Martin RJ, Rosenwasser LJ. Detection of alveolar macrophage-derived IL-1 beta in asthma. Inhibition with corticosteroids. J Immunol 1992;149:3078-3082.
16.Ludigs K, Parfenov V, Du Pasquier RA, Guarda G. Type I IFN-mediated regulation of IL-1 production in inflammatory disorders. Cell Mol Life Sci 2012;69:3395-3418.
17.Buettner R, Schölmerich J, Bollheimer LC. High‐fat diets: Modeling the metabolic disorders of human obesity in rodents. Obesity 2007;15:798-808.
18.Boskabady MH, Byrami G, Feizpour A. The effect of safranal, a constituent of Crocus sativus (saffron), on tracheal responsiveness, serum levels of cytokines, total NO and nitrite in sensitized guinea pigs. Pharmacol Rep 2014;66:56-61.
19.Xu C, Le J, Duan X, Du W, Liu B, Wu J, et al. Molecular mechanism of icariin on rat asthmatic model. Chin Med J 2011;124:2899-2906.
20.Otunola GA, Oloyede OB, Oladiji AT, Afolayan AA. Effects of diet-induced hypercholesterolemia on the lipid profile and some enzyme activities in female Wistar rats. Afr J Biochem Res 2010;4:149-154.
21.Hariri N, Thibault L. High-fat diet-induced obesity in animal models. Nutr Res Rev 2010;23:270-299.
22.Simson EL, Gold RM. The Lee obesity index vindicated? Physiol Behav 1982;29:371-376.
23.Alipour MR, Khamaneh AM, Yousefzadeh N, Mohammad-nejad D, Soufi FG. Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney. Mol Biol Rep 2013;40:6477-6483.
24.Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc 2008;3:1101-1108.
25.Galgani J, Ravussin E. Energy metabolism, fuel selection and body weight regulation. Int J Obes (Lond) 2008;32:S109-S119.
26.Farah CS, Salome CM. Asthma and obesity: a known association but unknown mechanism. Respirology. 2012;17:412-421.
27.Mancuso P. Obesity and lung inflammation. J Appl Physiol 2010;108:722-728.
28.Shore SA. Obesity and asthma: possible mechanisms. J Allergy Clin Immunol 2008;121:1087-1093.
29.Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362:801-809.
30.Johnson VJ, Yucesoy B, Luster MI. Prevention of IL-1 signaling attenuates airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate–induced asthma. J Allergy Clin Immunol 2005;116:851-858.
31.Shore SA, Moore PE. Effects of cytokines on contractile and dilator responses of airway smooth muscle. Clin Exp Pharmacol Physiol 2002;29:859-866.
32.Li T, Lu W-L, Hong H-Y, Yao Y-S, Han P, Li Z-K,  et al. Pharmacokinetics and anti-asthmatic potential of non-parenterally administered recombinant human interleukin-1 receptor antagonist in animal models. J Pharmacol Sci 2006;102:321-330.
33.Hakonarson H, Herrick DJ, Serrano PG, Grunstein MM. Autocrine role of interleukin 1beta in altered responsiveness of atopic asthmatic sensitized airway smooth muscle. J Clin Invest 1997;99:117.
34.Whelan R, Kim C, Chen M, Leiter J, Grunstein M, Hakonarson H. Role and regulation of interleukin-1 molecules in pro-asthmatic sensitised airway smooth muscle. Eur Respir J 2004;24:559-567.
35.Lu FL, Johnston RA, Flynt L, Theman TA, Terry RD, Schwartzman IN, et al. Increased pulmonary responses to acute ozone exposure in obese db/db mice. Am J Physiol Lung Cell Mol Physiol 2006;290:L856-L865.
36.Lee J-H, Wang L-C, Yu H-H, Lin Y-T, Yang Y-H, Chiang B-L. Type I IL-1 receptor (IL-1RI) as potential new therapeutic target for bronchial asthma. Mediators Inflamm 2010;2010.
37.Wesche H, Henzel WJ, Shillinglaw W, Li S, Cao Z. MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 1997;7:837-847.
38.Dinarello CA. Proinflammatory cytokines. Chest 2000;118:503-508.
39.McLachlan CR, Poulton R, Car G, Cowan J, Filsell S, Greene JM, et al. Adiposity, asthma, and airway inflammation. J Allergy Clin Immunol 2007;119:634-639.
40.Toru Ü, Ayada C, Genç O, Şahin S, Arık Ö, Acat, M, et al. Visfatin and ghrelin: can they be forthcoming biomarkers or new drug targets for asthma? Int J Clin Exp Med 2015;8: 6257–6261.
Iranian Journal of Basic Medical Sciences
Volume 19, Issue 4
April 2016
Pages 350-357

Files

Share

How to cite

Statistics