The Peroxisome Proliferator Activated Receptor Gamma (PPARγ) Ligand Rosiglitazone Modulates Bronchoalveolar Lavage Levels of Leptin, Adiponectin, and Inflammatory Cytokines in Lean and Obese Mice
Beiträge zur Klinik der Tuberkulose und spezifischen Tuberkulose-Forschung - Tập 185 - Trang 367-372 - 2007
Tóm tắt
Obese mice that lack leptin receptor (db
−
/db
−) have been shown to have innate bronchial hyperresponsiveness (BHR). It has been proposed that the obesity-mediated BHR may involve a combination of increased leptin and reduced systemic adiponectin levels. The aim of this study was to determine if obesity modifies the airway concentration of leptin and adiponectin and whether treatment with a synthetic peroxisome proliferator-activated receptor gamma (PPARγ) ligand can reduce airway leptin and increase airway adiponectin. In this study, obese, leptin receptor-deficient (db
−
/db
−), or lean (db
+
/db
−) mice were treated with rosiglitazone (3 mg/kg/day) or vehicle by gavage daily for 1 week. Bronchioalveolar lavage (BAL) was subsequently performed to determine levels of leptin, adiponectin, and inflammatory cytokines. Treatment with rosiglitazone increased BAL adiponectin levels in lean (p = 0.04) and to a lesser extent in obese mice (p = 0.07). Rosiglitazone treatment lowered leptin levels in lean mice, but increased leptin levels in BAL fluid of obese mice (p < 0.01). The BAL levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were lower in the lean rosiglitazone-treated group compared with the obese vehicle-treated group and lower in the obese rosiglitazone-treated group compared with the obese vehicle-treated group. These results demonstrate that obesity is associated with alterations in adipokine and cytokine levels in the airways that can be modulated by treatment with roziglitazone.
Tài liệu tham khảo
Beuther DA, Weiss ST, Sutherland ER (2006) Obesity and asthma. Am J Respir Crit Care Med 174(2):112–119
Shore SA (2006) Obesity and asthma: cause for concern. Curr Opin Pharmacol 6(3):230–236
Cassol V, Rizzato TM, Teche SP, Basso DF, Centenaro DF, Maldonado M, Moraes EZ, Hirakata VN, Sole D, Menna-Barreto SS (2006) Obesity and its relationship with asthma prevalence and severity in adolescents from southern Brazil. J Asthma 43(1):57–60
Akerman MJ, Calacanis CM, Madsen MK (2004) Relationship between asthma severity and obesity. J Asthma 41(5):521–526
Lavoie KL, Bacon SL, Labrecque M, Cartier A, Ditto B (2006) Higher BMI is associated with worse asthma control and quality of life but not asthma severity. Respir Med 100(4):648–657
Shore SA, Johnston RA (2006) Obesity and asthma. Pharmacol Ther 110(1):83–102
Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, Diehl AM (1998) Leptin regulates proinflammatory immune responses. FASEB J 12(1):57–65
Shore SA, Schwartzman IN, Mellema MS, Flynt L, Imrich A, Johnston RA (2005) Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol 115(1):103–109
Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, Mohlig M, Pfeiffer AF, Luft FC, Sharma AM (2003) Association between adiponectin and mediators of inflammation in obese women. Diabetes 52(4):942–947
Katsuki A, Suematsu M, Gabazza EC, Murashima S, Nakatani K, Togashi K, Yano Y, Adachi Y, Sumida Y (2006) Increased oxidative stress is associated with decreased circulating levels of adiponectin in Japanese metabolically obese, normal-weight men with normal glucose tolerance. Diabetes Res Clin Pract 73(3):310–314
Nakanishi S, Yamane K, Kamei N, Nojima H, Okubo M, Kohno N (2005) A protective effect of adiponectin against oxidative stress in Japanese Americans: the association between adiponectin or leptin and urinary isoprostane. Metabolism 54(2):194–199
Shore SA, Terry RD, Flynt L, Xu A, Hug C (2006) Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol 118(2):389–395
Shore SA, Rivera-Sanchez YM, Schwartzman IN, Johnston RA (2003) Responses to ozone are increased in obese mice. J Appl Physiol 95(3):938–945
Bruno A, Chanez P, Chiappara G, Siena L, Giammanco S, Gjomarkaj M, Bonsignore G, Bousquet J, Vignola AM (2005) Does leptin play a cytokine-like role within the airways of COPD patients? Eur Respir J 26(3):398–405
Decochez K, Rippley RK, Miller JL, De Smet M, Yan KX, Matthijs Z, Riffel KA, Song H, Zhu H, Maynor HO, Tanaka W, Johnson-Levonas AO, Davies MJ, Gottesdiener KM, Keymeulen B, Wagner JA (2006) A dual PPAR alpha/gamma agonist increases adiponectin and improves plasma lipid profiles in healthy subjects. Drugs R D 7(2):99–110
Tanko LB, Siddiq A, Lecoeur C, Larsen PJ, Christiansen C, Walley A, Froguel P (2005) ACDC/adiponectin and PPAR-gamma gene polymorphisms: implications for features of obesity. Obes Res 13(12):2113–2121
Tsuchida A, Yamauchi T, Takekawa S, Hada Y, Ito Y, Maki T, Kadowaki T (2005) Peroxisome proliferator-activated receptor (PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARalpha, PPARgamma, and their combination. Diabetes 54(12):3358–3370
Denning GM, Stoll LL (2006) Peroxisome proliferator-activated receptors: potential therapeutic targets in lung disease? Pediatr Pulmonol 41(1):23–34
Lee KS, Park SJ, Hwang PH, Yi HK, Song CH, Chai OH, Kim JS, Lee MK, Lee YC (2005) PPAR-gamma modulates allergic inflammation through up-regulation of PTEN. FASEB J 19(8):1033–1035
Honda K, Marquillies P, Capron M, Dombrowicz D (2004) Peroxisome proliferator-activated receptor gamma is expressed in airways and inhibits features of airway remodeling in a mouse asthma model. J Allergy Clin Immunol 113(5):882–888
Pershadsingh HA (2004) Peroxisome proliferator-activated receptor-gamma: therapeutic target for diseases beyond diabetes: quo vadis? Expert Opin Investig Drugs 13(3):215–228
Hammad H, de Heer HJ, Soullie T, Angeli V, Trottein F, Hoogsteden HC, Lambrecht BN (2004) Activation of peroxisome proliferator-activated receptor-gamma in dendritic cells inhibits the development of eosinophilic airway inflammation in a mouse model of asthma. Am J Pathol 164(1):263–271
Woerly G, Honda K, Loyens M, Papin JP, Auwerx J, Staels B, Capron M, Dombrowicz D (2003) Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation. J Exp Med 198(3):411–421
Liu MY, Xydakis AM, Hoogeveen RC, Jones PH, Smith EO, Nelson KW, Ballantyne CM (2005) Multiplexed analysis of biomarkers related to obesity and the metabolic syndrome in human plasma, using the Luminex-100 system. Clin Chem 51(7):1102–1109
Semple RK, Chatterjee VK, O’Rahilly S (2006) PPAR gamma and human metabolic disease. J Clin Invest 116(3):581–589
Kim SG, Ryu OH, Kim HY, Lee KW, Seo JA, Kim NH, Choi KM, Lee J, Baik SH, Choi DS (2006) Effect of rosiglitazone on plasma adiponectin levels and arterial stiffness in subjects with prediabetes or non-diabetic metabolic syndrome. Eur J Endocrinol 154(3):433–440
Toruner F, Akbay E, Cakir N, Sancak B, Elbeg S, Taneri F, Akturk M, Karakoc A, Ayvaz G, Arslan M (2004) Effects of PPARgamma and PPARalpha agonists on serum leptin levels in diet-induced obese rats. Horm Metab Res 36(4):226–230
Hwang J, Kleinhenz DJ, Rupnow HL, Campbell AG, Thule PM, Sutliff RL, Hart CM (2007) The PPARgamma ligand, rosiglitazone, reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice. Vascul Pharmacol 46(6):456–462
Cates EC, Fattouh R, Wattie J, Inman MD, Goncharova S, Coyle AJ, Gutierrez-Ramos JC, Jordana M (2004) Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism. J Immunol 173(10):6384–6392
Allakhverdi Z, Allam M, Renzi PM (2002) Inhibition of antigen-induced eosinophilia and airway hyperresponsiveness by antisense oligonucleotides directed against the common beta chain of IL-3, IL-5, GM-CSF receptors in a rat model of allergic asthma. Am J Respir Crit Care Med 165(7):1015–1021
Yamashita N, Tashimo H, Ishida H, Kaneko F, Nakano J, Kato H, Hirai K, Horiuchi T, Ohta K (2002) Attenuation of airway hyperresponsiveness in a murine asthma model by neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF). Cell Immunol 219(2):92–97
Turlej RK, Fiévez L, Sandersen CF, Dogné S, Kirschvink N, Lekeux P, Bureau F (2001) Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway. Thorax 56(9):696–702
Arnold R, Konig W (2006) Peroxisome-proliferator-activated receptor-gamma agonists inhibit the release of proinflammatory cytokines from RSV-infected epithelial cells. Virology 346(2):427–439
Conus S, Bruno A, Simon HU (2005) Leptin is an eosinophil survival factor. J Allergy Clin Immunol 116(6):1228–1234
Becker J, Delayre-Orthez C, Frossard N, Pons F (2006) Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases? Fundam Clin Pharmacol 20(5):429–447
Belvisi MG, Hele DJ, Birrell MA (2006) Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation. Eur J Pharmacol 533(1–3):101–109
Mueller C, Weaver V, Vanden Heuvel JP, August A, Cantorna MT (2003) Peroxisome proliferator-activated receptor gamma ligands attenuate immunological symptoms of experimental allergic asthma. Arch Biochem Biophys 418(2):186–196
Kobayashi M, Thomassen MJ, Rambasek T, Bonfield TL, Raychaudhuri B, Malur A, Winkler AR, Barna BP, Goldman SJ, Kavuru MS (2005) An inverse relationship between peroxisome proliferator-activated receptor gamma and allergic airway inflammation in an allergen challenge model. Ann Allergy Asthma Immunol 95(5):468–473
Benayoun L, Letuve S, Druilhe A, Boczkowski J, Dombret MC, Mechighel P, Megrel J, Leseche G, Aubier M, Pretolani M (2001) Regulation of peroxisome proliferator-activated receptor gamma expression in human asthmatic airways: relationship with proliferation, apoptosis, and airway remodeling. Am J Respir Crit Care Med 164(8 Pt 1):1487–1494
Cabrero A, Cubero M, Llaverias G, Alegret M, Sanchez R, Laguna JC, Vazquez-Carrera M (2005) Leptin down-regulates peroxisome proliferator-activated receptor gamma (PPAR-gamma) mRNA levels in primary human monocyte-derived macrophages. Mol Cell Biochem 275(1–2):173–179