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PPAR gamma activation following apoptotic cell instillation promotes resolution of lung inflammation and fibrosis via regulation of efferocytosis and proresolving cytokines

Title
PPAR gamma activation following apoptotic cell instillation promotes resolution of lung inflammation and fibrosis via regulation of efferocytosis and proresolving cytokines
Authors
Yoon, Y-SKim, S-YKim, M-JLim, J-HCho, M-SKang, J. L.
Ewha Authors
이지희
SCOPUS Author ID
이지희scopus
Issue Date
2015
Journal Title
MUCOSAL IMMUNOLOGY
ISSN
1933-0219JCR Link1935-3456JCR Link
Citation
vol. 8, no. 5, pp. 1031 - 1046
Publisher
NATURE PUBLISHING GROUP
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Changes in macrophage phenotype have been implicated in apoptotic cell-mediated immune modulation via induction of peroxisome proliferator-activated receptor-gamma (PPAR gamma). In this study, we characterized PPARc induction by apoptotic cell instillation over the course of bleomycin-induced lung injury in C57BL/6 mice. Next, the role of PPAR gamma activation in resolving lung inflammation and fibrosis was investigated. Our data demonstrate that apoptotic cell instillation after bleomycin results in immediate and prolonged enhancement of PPARc mRNA and protein in alveolar macrophages and lung. Moreover, PPAR gamma activity and expression of its target molecules, including CD36, macrophage mannose receptor, and arginase 1, were persistently enhanced following apoptotic cell instillation. Coadministration of the PPAR gamma antagonist, GW9662, reversed the enhanced efferocytosis, and the reduced proinflammatory cytokine expression, neutrophil recruitment, myeloperoxidase activity, hydroxyproline contents, and fibrosis markers, including type 1 collagen alpha 2, fibronectin and a-smooth muscle actin (alpha-SMA), in the lung by apoptotic cell instillation. In addition, inhibition of PPAR gamma activity reversed the expression of transforming growth factor-beta (TGF-beta), interleukin (IL)-10, and hepatocyte growth factor (HGF). These findings indicate that one-time apoptotic cell instillation contributes to anti-inflammatory and antifibrotic responses via upregulation of PPAR gamma expression and subsequent activation, leading to regulation of efferocytosis and production of proresolving cytokines.
DOI
10.1038/mi.2014.130
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의학전문대학원 > 의학과 > Journal papers
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