The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of intranasal rosiglitazone on airway inflammation and remodeling in a murine model of chronic asthma

  • Lee, Hwa Young (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Rhee, Chin Kook (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kang, Ji Young (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Park, Chan Kwon (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Lee, Sook Young (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kwon, Soon Suk (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kim, Young Kyoon (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Yoon, Hyoung Kyu (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
  • Received : 2014.08.13
  • Accepted : 2014.10.24
  • Published : 2016.01.01
⟨ Previous Next ⟩

Abstract

Background/Aims: Asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Peroxisome proliferator-activated receptors have been reported to regulate inflammatory responses in many cells. In this study, we examined the effects of intranasal rosiglitazone on airway remodeling in a chronic asthma model. Methods: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated intranasally with rosiglitazone with or without an antagonist during OVA challenge. We determined airway inflammation and the degree of airway remodeling by smooth muscle actin area and collagen deposition. Results: Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, compared with control mice. Additionally, the mice developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of rosiglitazone intranasally inhibited the eosinophilic inflammation significantly, and, importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. Expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) was increased in the OVA group and decreased in the rosiglitazone group. Co-treatment with GW9660 (a rosiglitazone antagonist) and rosiglitazone increased the expression of TLR-4 and $NF-{\kappa}B$. Conclusions: These results suggest that intranasal administration of rosiglitazone can prevent not only airway inf lammation but also airway remodeling associated with chronic allergen challenge. This beneficial effect is mediated by inhibition of TLR-4 and $NF-{\kappa}B$ pathways.

Keywords

References

  1. Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31:143-178. https://doi.org/10.1183/09031936.00138707
  2. Wiggs BR, Bosken C, Pare PD, James A, Hogg JC. A model of airway narrowing in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992;145:1251-1258. https://doi.org/10.1164/ajrccm/145.6.1251
  3. Zuyderduyn S, Sukkar MB, Fust A, Dhaliwal S, Burgess JK. Treating asthma means treating airway smooth muscle cells. Eur Respir J 2008;32:265-274. https://doi.org/10.1183/09031936.00051407
  4. Chan V, Burgess JK, Ratoff JC, et al. Extracellular matrix regulates enhanced eotaxin expression in asthmatic airway smooth muscle cells. Am J Respir Crit Care Med 2006;174:379-385. https://doi.org/10.1164/rccm.200509-1420OC
  5. Brightling CE, Ammit AJ, Kaur D, et al. The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. Am J Respir Crit Care Med 2005;171:1103-1108. https://doi.org/10.1164/rccm.200409-1220OC
  6. El-Shazly A, Berger P, Girodet PO, et al. Fraktalkine produced by airway smooth muscle cells contributes to mast cell recruitment in asthma. J Immunol 2006;176:1860-1868. https://doi.org/10.4049/jimmunol.176.3.1860
  7. Lazaar AL, Albelda SM, Pilewski JM, Brennan B, Pure E, Panettieri RA Jr. T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis. J Exp Med 1994;180:807-816. https://doi.org/10.1084/jem.180.3.807
  8. Hakonarson H, Kim C, Whelan R, Campbell D, Grunstein MM. Bi-directional activation between human airway smooth muscle cells and T lymphocytes: role in induction of altered airway responsiveness. J Immunol 2001;166:293-303. https://doi.org/10.4049/jimmunol.166.1.293
  9. Sukkar MB, Xie S, Khorasani NM, et al. Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle. J Allergy Clin Immunol 2006;118:641-648. https://doi.org/10.1016/j.jaci.2006.05.013
  10. Agrawal S, Agrawal A, Doughty B, et al. Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol 2003;171:4984-4989. https://doi.org/10.4049/jimmunol.171.10.4984
  11. 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;196:1645-1651. https://doi.org/10.1084/jem.20021340
  12. Shan X, Hu A, Veler H, et al. Regulation of Toll-like receptor 4-induced proasthmatic changes in airway smooth muscle function by opposing actions of ERK1/2 and p38 MAPK signaling. Am J Physiol Lung Cell Mol Physiol 2006;291:L324-L333. https://doi.org/10.1152/ajplung.00056.2006
  13. Belvisi MG, Hele DJ, Birrell MA. Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation. Eur J Pharmacol 2006;533:101-109. https://doi.org/10.1016/j.ejphar.2005.12.048
  14. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 1998;391:82-86. https://doi.org/10.1038/34184
  15. Bishop-Bailey D, Hla T. Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Delta12, 14-prostaglandin J2. J Biol Chem 1999;274:17042-17048. https://doi.org/10.1074/jbc.274.24.17042
  16. Rhee CK, Lee SY, Kang JY, et al. Effect of peroxisome proliferator-activated receptor-gamma on airway smooth muscle thickening in a murine model of chronic asthma. Int Arch Allergy Immunol 2009;148:289-296. https://doi.org/10.1159/000170382
  17. Shen Y, Chen L, Wang T, Wen F. $PPAR{\gamma}$ as a potential target to treat airway mucus hypersecretion in chronic airway inflammatory diseases. PPAR Res 2012;2012:256874.
  18. Zhu M, Flynt L, Ghosh S, et al. Anti-inflammatory effects of thiazolidinediones in human airway smooth muscle cells. Am J Respir Cell Mol Biol 2011;45:111-119. https://doi.org/10.1165/rcmb.2009-0445OC
  19. Patel HJ, Belvisi MG, Bishop-Bailey D, Yacoub MH, Mitchell JA. Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy. J Immunol 2003;170:2663-2669. https://doi.org/10.4049/jimmunol.170.5.2663
  20. Ji Y, Liu J, Wang Z, Liu N, Gou W. PPARgamma agonist, rosiglitazone, regulates angiotensin II-induced vascular inflammation through the TLR4-dependent signaling pathway. Lab Invest 2009;89:887-902. https://doi.org/10.1038/labinvest.2009.45
  21. Kruger NJ. The Bradford method for protein quantitation. Methods Mol Biol 1994;32:9-15.
  22. Rhee CK, Kim JW, Park CK, et al. Effect of imatinib on airway smooth muscle thickening in a murine model of chronic asthma. Int Arch Allergy Immunol 2011;155:243-251. https://doi.org/10.1159/000321261
  23. Inoue H, Tanabe T, Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma. J Biol Chem 2000;275:28028-28032.
  24. Trifilieff A, Bench A, Hanley M, Bayley D, Campbell E, Whittaker P. PPAR-alpha and -gamma but not -delta agonists inhibit airway inflammation in a murine model of asthma: in vitro evidence for an NF-kappaB-independent effect. Br J Pharmacol 2003;139:163-171. https://doi.org/10.1038/sj.bjp.0705232
  25. Honda K, Marquillies P, Capron M, Dombrowicz D. Peroxisome proliferator-activated receptor gamma is expressed in airways and inhibits features of airway remodeling in a mouse asthma model. J Allergy Clin Immunol 2004;113:882-888. https://doi.org/10.1016/j.jaci.2004.02.036
  26. Lee KS, Park SJ, Hwang PH, et al. PPAR-gamma modulates allergic inflammation through up-regulation of PTEN. FASEB J 2005;19:1033-1035. https://doi.org/10.1096/fj.04-3309fje
  27. Sun Y, Jia Z, Liu G, et al. $PPAR{\gamma}$ agonist rosiglitazone suppresses renal mpges-1/pge2 pathway in db/db mice. PPAR Res 2013;2013:612971.
  28. Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol 2012;188:21-28. https://doi.org/10.4049/jimmunol.1101029
  29. Scher JU, Pillinger MH. The anti-inflammatory effects of prostaglandins. J Investig Med 2009;57:703-708. https://doi.org/10.2310/JIM.0b013e31819aaa76
  30. Fogli S, Stefanelli F, Picchianti L, et al. Synergistic interaction between PPAR ligands and salbutamol on human bronchial smooth muscle cell proliferation. Br J Pharmacol 2013;168:266-275. https://doi.org/10.1111/j.1476-5381.2012.02180.x
  31. Stephen J, Delvecchio C, Spitale N, et al. PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis. Eur Respir J 2013;41:425-432. https://doi.org/10.1183/09031936.00145009
  32. Manuyakorn W, Howarth PH, Holgate ST. Airway remodelling in asthma and novel therapy. Asian Pac J Allergy Immunol 2013;31:3-10.
  33. Zhang LL, Gao CY, Fang CQ, et al. $PPAR{\gamma}$ attenuates intimal hyperplasia by inhibiting TLR4-mediated inflammation in vascular smooth muscle cells. Cardiovasc Res 2011;92:484-493. https://doi.org/10.1093/cvr/cvr238
  34. Wu Y, Zhao XD, Zhuang Z, et al. Peroxisome proliferator-activated receptor gamma agonist rosiglitazone attenuates oxyhemoglobin-induced Toll-like receptor 4 expression in vascular smooth muscle cells. Brain Res 2010;1322:102-108. https://doi.org/10.1016/j.brainres.2010.01.073
  35. Yin Y, Hou G, Li E, Wang Q, Kang J. $PPAR{\gamma}$ agonists regulate tobacco smoke-induced Toll like receptor 4 expression in alveolar macrophages. Respir Res 2014;15:28. https://doi.org/10.1186/1465-9921-15-28
  36. Dauphinee SM, Karsan A. Lipopolysaccharide signaling in endothelial cells. Lab Invest 2006;86:9-22. https://doi.org/10.1038/labinvest.3700366
  37. Hiatt WR, Kaul S, Smith RJ. The cardiovascular safety of diabetes drugs: insights from the rosiglitazone experience. N Engl J Med 2013;369:1285-1287. https://doi.org/10.1056/NEJMp1309610
  38. Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009;373:2125-2135. https://doi.org/10.1016/S0140-6736(09)60953-3

Cited by

  1. FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation vol.315, pp.2, 2018, https://doi.org/10.1152/ajplung.00429.2017
  2. NeTFactor, a framework for identifying transcriptional regulators of gene expression-based biomarkers vol.9, pp.None, 2016, https://doi.org/10.1038/s41598-019-49498-y
  3. Chinese Herbs and Repurposing Old Drugs as Therapeutic Agents in the Regulation of Oxidative Stress and Inflammation in Pulmonary Diseases vol.14, pp.None, 2016, https://doi.org/10.2147/jir.s293135
  4. Beyond TGFβ1 - novel treatment strategies targeting lung fibrosis vol.141, pp.None, 2021, https://doi.org/10.1016/j.biocel.2021.106090
  5. Tiotropium Bromide Has a More Potent Effect Than Corticosteroid in the Acute Neutrophilic Asthma Mouse Model vol.85, pp.1, 2016, https://doi.org/10.4046/trd.2021.0118