UNASSIGNED: COPD is a highly prevalent, chronic @entity55 with limited existing therapeutic options. While modulation of @entity3229 ( @entity3229 ) y activity can modify inflammatory responses in several models of @entity651 , the relevance of @entity12097 pathway in COPD pathogenesis has not been previously explored. @entity19 lacking @entity12097 specifically in airway epithelial cells displayed increased susceptibility to chronic cigarette smoke (CS)-induced @entity2415 , with excessive macrophage accumulation associated with increased expression of chemokines, @entity638 , @entity15369 and @entity3806 . Conversely, treatment of @entity19 with a pharmacological PPARy activator attenuated @entity15369 and @entity3806 expression and macrophage accumulation in response to CS. In vitro, CS increased lung epithelial cell chemokine expression in a PPARy-activation dependent fashion. The ability of PPARy to regulate CS-induced chemokine expression in vitro was not specifically associated with peroxisome proliferator response element (PPRE)-mediated trans-activation activity, but was correlated with PPARy-mediated trans-repression of NF-kB activity. Pharmacological or genetic activation of PPARy activity abrogated CS-dependent induction of NF-kB activity, while inhibition of PPARy activity enhanced CS-induced NF-kB activity. Regulation of NF-kB activity involved direct PPARy-NF-kB interaction and PPARy-mediated effects on IKK activation, IkBa degradation and nuclear translocation of @entity1992 . Our data indicate that @entity12097 represents a disease-relevant pathophysiological and pharmacological target in COPD. Its activation state likely contributes to NF-kB -dependent, CS-induced chemokine-mediated regulation of inflammatory cell accumulation.

Airway Epithelial Cell PPARy Modulates Cigarette Smoke Induced Chemokine Expression and Emphysema Susceptibility In XXXX .

@entity12097 :: ('19016(Tax:10090)', 'Gene') :: ['PPARG', 'Pparg'] @entity1992 :: ('19697(Tax:10090)', 'Gene') :: ['p65'] @entity3229 :: ('19013(Tax:10090)', 'Gene') :: ['PPAR', 'peroxisome proliferator-activating receptor'] @entity55 :: ('MESH:D011014', 'Disease') :: ['inflammatory lung disease'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mice'] @entity3806 :: ('20309(Tax:10090)', 'Gene') :: ['Cxcl15'] @entity2415 :: ('MESH:D004646', 'Disease') :: ['emphysema'] @entity651 :: ('MESH:D055370', 'Disease') :: ['lung injury'] @entity638 :: ('20304(Tax:10090)', 'Gene') :: ['Ccl5'] @entity15369 :: ('15945(Tax:10090)', 'Gene') :: ['Cxcl10']
@entity19 :: (10090,Species) :: ['Mice']
