Interaction of Apoptotic Cells with Macrophages Upregulates COX-2/PGE(2) and HGF Expression via a Positive Feedback Loop
- 등재 SCIE, SCOPUS
- 발행기관 HINDAWI PUBLISHING CORPORATION
- 발행년도 2014
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000091174
- 본문언어 영어
- Published As http://dx.doi.org/10.1155/2014/463524
초록/요약
Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE(2)) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE(2) expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE(2) and HGF signaling pathways. Exposure of RAW264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE(2). The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE(2) production. Both NS-398 and COX-2- siRNA, as well as the PGE(2) receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE(2) induction. The in vivo relevance of the interaction between the COX-2/PGE(2) and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE(2) and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition.
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