Distinct Roles for the A2B Adenosine Receptor in Acute and Chronic Stages of Bleomycin-Induced Lung Injury
作者： Yang Zhou , Daniel J. Schneider , Eva Morschl , Ling Song , Mesias Pedroza
关键词:
摘要: Adenosine is an extracellular signaling molecule that generated in response to cell injury where it orchestrates tissue protection and repair. Whereas adenosine best known for promoting anti-inflammatory activities during acute responses, prolonged elevations can enhance destructive remodeling processes associated with chronic disease states. The generation of the subsequent activation 2B receptor (A2BR) important regulation both lung disease. goal this study was examine contribution A2BR models bleomycin-induced exhibit varying degrees injury. Intratracheal bleomycin exposure results substantial followed by progressive fibrosis. In model, genetic removal resulted enhanced loss barrier function increased pulmonary inflammation, few differences indexes These support role model contrast, systemic mice modest together effects on were negligible; however, there reductions fibrosis, supporting a profibrotic receptor. A2BR-dependent IL-6 production identified as potential mechanism involved diminished fibrosis seen knockout exposed i.p. bleomycin. studies highlight distinct roles stages
jimmunol.org参考文章(51)
Yang Zhou, Jayasimha N. Murthy, Dewan Zeng, Luiz Belardinelli, Michael R. Blackburn, Alterations in Adenosine Metabolism and Signaling in Patients with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis PLoS ONE. ,vol. 5, pp. e9224- ,(2010) , 10.1371/JOURNAL.PONE.0009224
K. K. Kim, M. C. Kugler, P. J. Wolters, L. Robillard, M. G. Galvez, A. N. Brumwell, D. Sheppard, H. A. Chapman, Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix Proceedings of the National Academy of Sciences of the United States of America. ,vol. 103, pp. 13180- 13185 ,(2006) , 10.1073/PNAS.0605669103
Chun-Xiao Sun, Hongyan Zhong, Amir Mohsenin, Eva Morschl, Janci L Chunn, Jose G Molina, Luiz Belardinelli, Dewan Zeng, Michael R Blackburn, Role of A2B adenosine receptor signaling in adenosine-dependent pulmonary inflammation and injury Journal of Clinical Investigation. ,vol. 116, pp. 2173- 2182 ,(2006) , 10.1172/JCI27303
P J Sime, Z Xing, F L Graham, K G Csaky, J Gauldie, Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. Journal of Clinical Investigation. ,vol. 100, pp. 768- 776 ,(1997) , 10.1172/JCI119590
Tobias Eckle, Marion Faigle, Almut Grenz, Stefanie Laucher, Linda F. Thompson, Holger K. Eltzschig, A2B adenosine receptor dampens hypoxia-induced vascular leak Blood. ,vol. 111, pp. 2024- 2035 ,(2008) , 10.1182/BLOOD-2007-10-117044
T Ashcroft, J M Simpson, V Timbrell, Simple method of estimating severity of pulmonary fibrosis on a numerical scale. Journal of Clinical Pathology. ,vol. 41, pp. 467- 470 ,(1988) , 10.1136/JCP.41.4.467
John Hay, Shahriar Shahzeidi, Geoffrey Laurent, MECHANISMS OF BLEOMYCIN-INDUCED LUNG DAMAGE Archives of Toxicology. ,vol. 65, pp. 81- 94 ,(1991) , 10.1007/BF02034932
Tianqing Kong, Karen A. Westerman, Marion Faigle, Holger K. Eltzschig, Sean P. Colgan, HIF-dependent induction of adenosine A2B receptor in hypoxia The FASEB Journal. ,vol. 20, pp. 2242- 2250 ,(2006) , 10.1096/FJ.06-6419COM
Carol M. Aherne, Emily M. Kewley, Holger K. Eltzschig, The resurgence of A2B adenosine receptor signaling. Biochimica et Biophysica Acta. ,vol. 1808, pp. 1329- 1339 ,(2011) , 10.1016/J.BBAMEM.2010.05.016
Balázs Csóka, Zoltán H Németh, Peter Rosenberger, Holger K Eltzschig, Zoltán Spolarics, Pál Pacher, Zsolt Selmeczy, Balázs Koscsó, Leonóra Himer, E Sylvester Vizi, Michael R Blackburn, Edwin A Deitch, György Haskó, None, A2B adenosine receptors protect against sepsis-induced mortality by dampening excessive inflammation Journal of Immunology. ,vol. 185, pp. 542- 550 ,(2010) , 10.4049/JIMMUNOL.0901295