Airway epithelial cell PPARγ modulates cigarette smoke-induced chemokine expression and emphysema susceptibility in mice

American Journal of Physiology - Lung Cellular and Molecular Physiology

Volumn 309, Issue 3, 2015, Pages L293-L304

  Kumar Solleti, Siva ^a   Simon, Dawn M ^b   Srisuma, Sorachai ^c   Arikan, Meltem C ^d   Bhattacharya, Soumyaroop ^a   Rangasamy, Tirumalai ^a   Bijli, Kaiser M ^a,f   Rahman, Arshad ^a   Crossno, Joseph T ^e   Shapiro, Steven D ^g   Mariani, Thomas J ^a  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^b The Apnea Center   (United States)

^c MAHIDOL UNIVERSITY   (Thailand)

^d HARVARD MEDICAL SCHOOL   (United States)

^e UNIVERSITY OF COLORADO   (United States)

^f EMORY UNIVERSITY   (United States)

^g UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

Chronic obstructive pulmonary disease; Lung inflammation; Nuclear factor kB; Peroxisome proliferator activating receptor ; Rosiglita zone

Indexed keywords

CHEMOKINE; CIGARETTE SMOKE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PEROXISOME PROLIFERATOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONTROLLED STUDY; DISEASE PREDISPOSITION; GENE ACTIVATION; GENE CONTROL; LUNG EMPHYSEMA; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RESPIRATORY EPITHELIUM; TRANSACTIVATION; 129 MOUSE; ADVERSE EFFECTS; ANIMAL; C57BL MOUSE; CELL LINE; FEMALE; IMMUNOLOGY; METABOLISM; PHYSIOLOGY; PULMONARY EMPHYSEMA; SIGNAL TRANSDUCTION; SMOKING; TRANSCRIPTION INITIATION;

ANIMALS; CELL LINE; CHEMOKINES; DISEASE SUSCEPTIBILITY; FEMALE; MICE, 129 STRAIN; MICE, INBRED C57BL; NF-KAPPA B; PPAR GAMMA; PULMONARY EMPHYSEMA; SIGNAL TRANSDUCTION; SMOKING; TRANSCRIPTIONAL ACTIVATION;

EID: 84938582355     PISSN: 10400605     EISSN: 15221504     Source Type: Journal    
DOI: 10.1152/ajplung.00287.2014     Document Type: Article

References (91)

1. Akiyama TE, Sakai S, Lambert G, Nicol CJ, Matsusue K, Pimprale S, Lee YH, Ricote M, Glass CK, Brewer HB Jr, Gonzalez FJ. Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Mol Cell Biol 22: 2607–2619, 2002.
2. Amoruso A, Bardelli C, Gunella G, Fresu LG, Ferrero V, Brunelleschi S. Quantification of PPAR-gamma protein in monocyte/macrophages from healthy smokers and non-smokers: a possible direct effect of nicotine. Life Sci 81: 906–915, 2007.
3. Anto RJ, Mukhopadhyay A, Shishodia S, Gairola CG, Aggarwal BB. Cigarette smoke condensate activates nuclear transcription factor-kappaB through phosphorylation and degradation of IkappaB(alpha): correlation with induction of cyclooxygenase-2. Carcinogenesis 23: 1511–1518, 2002.
4. Aoshiba K, Yokohori N, Nagai A. Alveolar wall apoptosis causes lung destruction and emphysematous changes. Am J Respir Cell Mol Biol 28: 555–562, 2003.
5. Bailey ST, Ghosh S. ‘PPAR’ting ways with inflammation. Nat Immunol 6: 966–967, 2005.
6. Barak Y, Nelson MC, Ong ES, Jones YZ, Ruiz-Lozano P, Chien KR, Koder A, Evans RM. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 4: 585–595, 1999.
7. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 8: 183–192, 2008.
8. Belvisi MG, Hele DJ, Birrell MA. Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation. Eur J Pharmacol 533: 101–109, 2006.
9. Benayoun L, Letuve S, Druilhe A, Boczkowski J, Dombret MC, Mechighel P, Megret J, Leseche G, Aubier M, Pretolani M. 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: 1487–1494, 2001.
10. Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 53: 409–435, 2002.
11. Birrell MA, Patel HJ, McCluskie K, Wong S, Leonard T, Yacoub MH, Belvisi MG. PPAR-gamma agonists as therapy for diseases involving airway neutrophilia. Eur Respir J 24: 18–23, 2004.
12. Bracke KR, D’Hulst AI, Maes T, Moerloose KB, Demedts IK, Lebecque S, Joos GF, Brusselle GG. Cigarette smoke-induced pulmonary inflammation and emphysema are attenuated in CCR6-deficient mice. J Immunol 177: 4350–4359, 2006.
13. Cavarra E, Bartalesi B, Lucattelli M, Fineschi S, Lunghi B, Gambelli F, Ortiz LA, Martorana PA, Lungarella G. Effects of cigarette smoke in mice with different levels of alpha(1)-proteinase inhibitor and sensitivity to oxidants. Am J Respir Crit Care Med 164: 886–890, 2001.
14. Chen SC, Mehrad B, Deng JC, Vassileva G, Manfra DJ, Cook DN, Wiekowski MT, Zlotnik A, Standiford TJ, Lira SA. Impaired pulmonary host defense in mice lacking expression of the CXC chemokine lungkine. J Immunol 166: 3362–3368, 2001.
15. Cheng DS, Han W, Chen SM, Sherrill TP, Chont M, Park GY, Sheller JR, Polosukhin VV, Christman JW, Yull FE, Blackwell TS. Airway epithelium controls lung inflammation and injury through the NF-kappa B pathway. J Immunol 178: 6504–6513, 2007.
16. Chinetti G, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors and inflammation: from basic science to clinical applications. Int J Obes Relat Metab Disord 27, Suppl 3: S41–S45, 2003.
17. Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, Torra IP, Teissier E, Minnich A, Jaye M, Duverger N, Brewer HB, Fruchart JC, Clavey V, Staels B. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 7: 53–58, 2001.
18. Cokkinides V, Bandi P, McMahon C, Jemal A, Glynn T, Ward E. Tobacco control in the United States–recent progress and opportunities. CA Cancer J Clin 59: 352–365, 2009.
19. Corton JC, Lapinskas PJ, Gonzalez FJ. Central role of PPARalpha in the mechanism of action of hepatocarcinogenic peroxisome proliferators. Mutat Res 448: 139–151, 2000.
20. Couillin I, Vasseur V, Charron S, Gasse P, Tavernier M, Guillet J, Lagente V, Fick L, Jacobs M, Coelho FR, Moser R, Ryffel B. IL-1R1/MyD88 signaling is critical for elastase-induced lung inflammation and emphysema. J Immunol 183: 8195–8202, 2009.
21. Crossno JT Jr, Garat CV, Reusch JE, Morris KG, Dempsey EC, McMurtry IF, Stenmark KR, Klemm DJ. Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodeling. Am J Physiol Lung Cell Mol Physiol 292: L885–L897, 2007.
22. Daynes RA, Jones DC. Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2: 748–759, 2002.
23. Delerive P, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol 169: 453–459, 2001.
24. Di Paola R, Mazzon E, Maiere D, Zito D, Britti D, De Majo M, Genovese T, Cuzzocrea S. Rosiglitazone reduces the evolution of experimental periodontitis in the rat. J Dent Res 85: 156–161, 2006.
25. Di Stefano A, Caramori G, Gnemmi I, Contoli M, Bristot L, Capelli A, Ricciardolo FL, Magno F, D’Anna SE, Zanini A, Carbone M, Sabatini F, Usai C, Brun P, Chung KF, Barnes PJ, Papi A, Adcock IM, Balbi B. Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD. Thorax 64: 968–975, 2009.
26. Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M. Identification of nuclear receptor corepressor as a peroxisome proliferatoractivated receptor alpha interacting protein. J Biol Chem 274: 15901–15907, 1999.
27. Gamble E, Grootendorst DC, Hattotuwa K, O’Shaughnessy T, Ram FS, Qiu Y, Zhu J, Vignola AM, Kroegel C, Morell F, Pavord ID, Rabe KF, Jeffery PK, Barnes NC. Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis. Eur Respir J 30: 467–471, 2007.
28. Genovese T, Cuzzocrea S, Di Paola R, Mazzon E, Mastruzzo C, Catalano P, Sortino M, Crimi N, Caputi AP, Thiemermann C, Vancheri C. Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury. Eur Respir J 25: 225–234, 2005.
29. Ghisletti S, Huang W, Ogawa S, Pascual G, Lin ME, Willson TM, Rosenfeld MG, Glass CK. Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Mol Cell 25: 57–70, 2007.
30. Giaginis C, Giagini A, Theocharis S. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands as potential therapeutic agents to treat arthritis. Pharmacol Res 60: 160–169, 2009.
31. Giovino GA. The tobacco epidemic in the United States. Am J Prev Med 33: S318–S326, 2007.
32. Glass CK, Ogawa S. Combinatorial roles of nuclear receptors in inflammation and immunity. Nat Rev Immunol 6: 44–55, 2006.
33. Grumelli S, Corry DB, Song LZ, Song L, Green L, Huh J, Hacken J, Espada R, Bag R, Lewis DE, Kheradmand F. An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema. PLoS Med 1: e8, 2004.
34. Guerassimov A, Hoshino Y, Takubo Y, Turcotte A, Yamamoto M, Ghezzo H, Triantafillopoulos A, Whittaker K, Hoidal JR, Cosio MG. The development of emphysema in cigarette smoke-exposed mice is strain dependent. Am J Respir Crit Care Med 170: 974–980, 2004.
35. Gurnell M, Wentworth JM, Agostini M, Adams M, Collingwood TN, Provenzano C, Browne PO, Rajanayagam O, Burris TP, Schwabe JW, Lazar MA, Chatterjee VK. A dominant-negative peroxisome proliferator-activated receptor gamma (PPARgamma) mutant is a constitutive repressor and inhibits PPARgamma-mediated adipogenesis. J Biol Chem 275: 5754–5759, 2000.
36. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 277: 2002–2004, 1997.
37. Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell 132: 344–362, 2008.
38. Huang TH, Razmovski-Naumovski V, Kota BP, Lin DS, Roufogalis BD. The pathophysiological function of peroxisome proliferator-activated receptor-gamma in lung-related diseases (Abstract). Respir Res 6: 102, 2005.
39. Jennewein C, Kuhn AM, Schmidt MV, Meilladec-Jullig V, von Knethen A, Gonzalez FJ, Brune B. Sumoylation of peroxisome proliferator- activated receptor gamma by apoptotic cells prevents lipopolysaccharide- induced NCoR removal from kappaB binding sites mediating transrepression of proinflammatory cytokines. J Immunol 181: 5646–5652, 2008.
40. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391: 82–86, 1998.
41. Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, Waltenberger J, Voelkel NF. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 106: 1311–1319, 2000.
42. Katayama K, Wada K, Nakajima A, Mizuguchi H, Hayakawa T, Nakagawa S, Kadowaki T, Nagai R, Kamisaki Y, Blumberg RS, Mayumi T. A novel PPAR gamma gene therapy to control inflammation associated with inflammatory bowel disease in a murine model. Gastroenterology 124: 1315–1324, 2003.
43. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature 405: 421–424, 2000.
44. Kubota N, Terauchi Y, Miki H, Tamemoto H, Yamauchi T, Komeda K, Satoh S, Nakano R, Ishii C, Sugiyama T, Eto K, Tsubamoto Y, Okuno A, Murakami K, Sekihara H, Hasegawa G, Naito M, Toyoshima Y, Tanaka S, Shiota K, Kitamura T, Fujita T, Ezaki O, Aizawa S, Kadowaki T. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 4: 597–609, 1999.
45. Lakatos HF, Thatcher TH, Kottmann RM, Garcia TM, Phipps RP, Sime PJ. The role of PPARs in lung fibrosis (Abstract). PPAR Res 2007: 71323, 2007.
46. Lapperre TS, Postma DS, Gosman MM, Snoeck-Stroband JB, ten Hacken NH, Hiemstra PS, Timens W, Sterk PJ, Mauad T. Relation between duration of smoking cessation and bronchial inflammation in COPD. Thorax 61: 115–121, 2006.
47. Lee S, Kim W, Moon SO, Sung MJ, Kim DH, Kang KP, Jang YB, Lee JE, Jang KY, Park SK. Rosiglitazone ameliorates cisplatin-induced renal injury in mice. Nephrol Dial Transplant 21: 2096–2105, 2006.
48. Lee SY, Kang EJ, Hur GY, Jung KH, Jung HC, Lee SY, Kim JH, Shin C, In KH, Kang KH, Yoo SH, Shim JJ. Peroxisome proliferatoractivated receptor-gamma inhibits cigarette smoke solution-induced mucin production in human airway epithelial (NCI-H292) cells. Am J Physiol Lung Cell Mol Physiol 291: L84–L90, 2006.
49. Li AC, Palinski W. Peroxisome proliferator-activated receptors: how their effects on macrophages can lead to the development of a new drug therapy against atherosclerosis. Annu Rev Pharmacol Toxicol 46: 1–39, 2006.
50. Maeno T, Houghton AM, Quintero PA, Grumelli S, Owen CA, Shapiro SD. CD8 T Cells are required for inflammation and destruction in cigarette smoke-induced emphysema in mice. J Immunol 178: 8090–8096, 2007.
51. Minhajuddin M, Fazal F, Bijli KM, Amin MR, Rahman A. Inhibition of mammalian target of rapamycin potentiates thrombin-induced intercellular adhesion molecule-1 expression by accelerating and stabilizing NF-kappa B activation in endothelial cells. J Immunol 174: 5823–5829, 2005.
52. Nie L, Xiang R, Zhou W, Lu B, Cheng D, Gao J. Attenuation of acute lung inflammation induced by cigarette smoke in CXCR3 knockout mice (Abstract). Respir Res 9: 82, 2008.
53. Paola RD, Cuzzocrea S. Peroxisome proliferator-activated receptors and acute lung injury (Abstract). PPAR Res 2007: 63745, 2007.
54. Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, Willson TM, Rosenfeld MG, Glass CK. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437: 759–763, 2005.
55. 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 cortico- steroids: relevance for chronic obstructive pulmonary disease therapy. J Immunol 170: 2663–2669, 2003.
56. Pauwels RA, Buist AS, Ma P, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD): executive summary. Respir Care 46: 798–825, 2001.
57. Perez A, van Heeckeren AM, Nichols D, Gupta S, Eastman JF, Davis PB. Peroxisome proliferator-activated receptor-gamma in cystic fibrosis lung epithelium. Am J Physiol Lung Cell Mol Physiol 295: L303–L313, 2008.
58. Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8: 49–62, 2007.
59. Perl AK, Zhang L, Whitsett JA. Conditional expression of genes in the respiratory epithelium in transgenic mice: cautionary notes and toward building a better mouse trap. Am J Respir Cell Mol Biol 40: 1–3, 2009.
60. Ramakers JD, Verstege MI, Thuijls G, Te Velde AA, Mensink RP, Plat J. The PPARgamma agonist rosiglitazone impairs colonic inflammation in mice with experimental colitis. J Clin Immunol 27: 275–283, 2007.
61. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391: 79–82, 1998.
62. Rossi DL, Hurst SD, Xu Y, Wang W, Menon S, Coffman RL, Zlotnik A. Lungkine, a novel CXC chemokine, specifically expressed by lung bronchoepithelial cells. J Immunol 162: 5490–5497, 1999.
63. Saetta M, Mariani M, Panina-Bordignon P, Turato G, Buonsanti C, Baraldo S, Bellettato CM, Papi A, Corbetta L, Zuin R, Sinigaglia F, Fabbri LM. Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 165: 1404–1409, 2002.
64. Schaiff WT, Carlson MG, Smith SD, Levy R, Nelson DM, Sadovsky Y. Peroxisome proliferator-activated receptor-gamma modulates differentiation of human trophoblast in a ligand-specific manner. J Clin Endocrinol Metab 85: 3874–3881, 2000.
65. Schneider D, Ganesan S, Comstock AT, Meldrum CA, Mahidhara R, Goldsmith AM, Curtis JL, Martinez FJ, Hershenson MB, Sajjan U. Increased cytokine response of rhinovirus-infected airway epithelial cells in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 182: 332–340, 200.
66. Serhan CN, Devchand PR. Novel antiinflammatory targets for asthma. A role for PPARgamma? Am J Respir Cell Mol Biol 24: 658–661, 2001.
67. Shan M, You R, Yuan X, Frazier MV, Porter P, Seryshev A, Hong JS, Song LZ, Zhang Y, Hilsenbeck S, Whitehead L, Zarinkamar N, Perusich S, Corry DB, Kheradmand F. Agonistic induction of PPARgamma reverses cigarette smoke-induced emphysema. J Clin Invest 124: l1371–1381, 200
68. Shishodia S, Aggarwal BB. Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates activation of cigarette smoke-induced nuclear factor (NF)-kappaB by suppressing activation of IkappaBalpha kinase in human non-small cell lung carcinoma: correlation with suppression of cyclin D1, COX-2, and matrix metalloproteinase-9. Cancer Res 64: 5004–5012, 2004.
69. Simon DM, Arikan MC, Srisuma S, Bhattacharya S, Tsai LW, Ingenito EP, Gonzalez F, Shapiro SD, Mariani TJ. Epithelial cell PPAR-[gamma] contributes to normal lung maturation. FASEB J 20: 1507–1509, 2006.
70. Simon DM, Tsai LW, Ingenito EP, Starcher BC, Mariani TJ. PPARgamma deficiency results in reduced lung elastic recoil and abnormalities in airspace distribution (Abstract). Respir Res 11: 69, 2000.
71. Skerrett SJ, Liggitt HD, Hajjar AM, Ernst RK, Miller SI, Wilson CB. Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin. Am J Physiol Lung Cell Mol Physiol 287: L143–L152, 2004.
72. Spears M, McSharry C, Thomson NC. Peroxisome proliferator-activated receptor-gamma agonists as potential anti-inflammatory agents in asthma and chronic obstructive pulmonary disease. Clin Exp Allergy 36: 1494–1504, 2006.
73. Srisuma S, Bhattacharya S, Simon DM, Solleti SK, Tyagi S, Starcher B, Mariani TJ. Fibroblast growth factor receptors control epithelialmesenchymal interactions necessary for alveolar elastogenesis. Am J Respir Crit Care Med 181: 838–850, 200.
74. Standiford TJ, Keshamouni VG, Reddy RC. Peroxisome proliferatoractivated receptor-γ as a regulator of lung inflammation and repair. Proc Am Thorac Soc 2: 226–231, 2005.
75. Straus DS, Pascual G, Li M, Welch JS, Ricote M, Hsiang CH, Sengchanthalangsy LL, Ghosh G, Glass CK. 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signalling pathway. Proc Natl Acad Sci USA 97: 4844–4849, 2000.
76. Takaki K, Mitsuyama K, Tsuruta O, Toyonaga A, Sata M. Attenuation of experimental colonic injury by thiazolidinedione agents. Inflamm Res 55: 10–15, 2006.
77. Taraseviciene-Stewart L, Voelkel NF. Molecular pathogenesis of emphysema. J Clin Invest 118: 394–402, 2008.
78. Thorley AJ, Tetley TD. Pulmonary epithelium, cigarette smoke, and chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2: 409–428, 2007.
79. Tuder RM, McGrath S, Neptune E. The pathobiological mechanisms of emphysema models: what do they have in common? Pulm Pharmacol Ther 16: 67–78, 2003.
80. Turato G, Di Stefano A, Maestrelli P, Mapp CE, Ruggieri MP, Roggeri A, Fabbri LM, Saetta M. Effect of smoking cessation on airway inflammation in chronic bronchitis. Am J Respir Crit Care Med 152: 1262–1267, 1995.
81. Vamecq J, Latruffe N. Medical significance of peroxisome proliferatoractivated receptors. Lancet 354: 141–148, 1999.
82. Verges B. Clinical interest of PPARs ligands. Diabetes Metab 30: 7–12, 2004.
83. Wang AC, Dai X, Luu B, Conrad DJ. Peroxisome proliferator-activated receptor-gamma regulates airway epithelial cell activation. Am J Respir Cell Mol Biol 24: 688–693, 2001.
84. Ward JE, Fernandes DJ, Taylor CC, Bonacci JV, Quan L, Stewart AG. The PPARgamma ligand, rosiglitazone, reduces airways hyperresponsiveness in a murine model of allergen-induced inflammation. Pulm Pharmacol Ther 19: 39–46, 2006.
85. Ward JE, Tan X. Peroxisome proliferator activated receptor ligands as regulators of airway inflammation and remodelling in chronic lung disease (Abstract). PPAR Res 2007: 14983, 2007.
86. White WB. Smoking-related morbidity and mortality in the cardiovascular setting. Prev Cardiol 10: 1–4, 2007.
87. Woerly G, Honda K, Loyens M, Papin JP, Auwerx J, Staels B, Capron M, Dombrowicz D. Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation. J Exp Med 198: 411–421, 2003.
88. Wu L, Wang G, Qu P, Yan C, Du H. Overexpression of dominant negative peroxisome proliferator-activated receptor-gamma (PPARgamma) in alveolar type II epithelial cells causes inflammation and T-cell suppression in the lung. Am J Pathol 178: 2191–2204.
89. Yang SR, Chida AS, Bauter MR, Shafiq N, Seweryniak K, Maggirwar SB, Kilty I, Rahman I. Cigarette smoke induces proinflammatory cytokine release by activation of NF-kappaB and posttranslational modifications of histone deacetylase in macrophages. Am J Physiol Lung Cell Mol Physiol 291: L46–L57, 2006.
90. 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 15: 28, 2014.
91. Zheng T, Kang MJ, Crothers K, Zhu Z, Liu W, Lee CG, Rabach LA, Chapman HA, Homer RJ, Aldous D, De Sanctis GT, Underwood S, Graupe M, Flavell RA, Schmidt JA, Elias JA. Role of cathepsin S-dependent epithelial cell apoptosis in IFN-gamma-induced alveolar remodeling and pulmonary emphysema. J Immunol 174: 8106–8115, 2005.