Interaction of apoptotic cells with macrophages upregulates COX-2/PGE2 and HGF expression via a positive feedback loop.
Interaction of apoptotic cells with macrophages upregulates COX-2/PGE2 and HGF expression via a positive feedback loop.
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DOI：
10.1155/2014/463524
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发表时间：
2014
影响因子：
4.6
通讯作者：
Kang JL
中科院分区：
文献类型：
--
作者：
Byun JY;Youn YS;Lee YJ;Choi YH;Woo SY;Kang JL
巨噬细胞对凋亡细胞的识别对于解决炎症、免疫耐受和组织修复至关重要。环氧合酶-2（考克斯-2）/前列腺素E2（PGE 2）和肝细胞生长因子（HGF）在组织修复过程中起重要作用。我们研究了凋亡细胞介导的巨噬细胞考克斯-2和PGE 2表达的特征，然后确定巨噬细胞如何在体外和体内暴露于凋亡细胞，协调考克斯-2/PGE 2和HGF信号通路之间的相互作用。RAW 264.7细胞和原代腹腔巨噬细胞暴露于凋亡细胞导致考克斯-2和PGE 2的诱导。考克斯-2抑制剂NS-398抑制凋亡细胞诱导的PGE 2产生。NS-398和考克斯-2-siRNA以及PGE 2受体EP 2拮抗剂均阻断了响应凋亡细胞的HGF表达。此外，HGF受体拮抗剂抑制考克斯-2和PGE 2诱导的增加。在博来霉素刺激的肺体内暴露于凋亡细胞后，在培养的肺泡巨噬细胞中显示了考克斯-2/PGE 2和HGF途径之间通过正反馈回路的相互作用的体内相关性。我们的研究结果表明，上调的考克斯-2/PGE 2和HGF的巨噬细胞暴露于凋亡细胞后，代表了一种机制，介导的抗炎和抗纤维化的后果凋亡细胞识别。
Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 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/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 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/PGE2 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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影响因子：
5.5
作者：
Park, Hyun-Jung;Choi, Youn-Hee;Kang, Jihee Lee
通讯作者：
Kang, Jihee Lee
DOI：
10.2183/pjab.86.588
发表时间：
2010
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Nakamura T;Mizuno S
通讯作者：
Mizuno S
影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
4.4
作者：
White, Kimberly E.;Ding, Qiang;Olman, Mitchell A.
通讯作者：
Olman, Mitchell A.
影响因子：
13.5
作者：
Kosai, K;Matsumoto, K;Nakamura, T
通讯作者：
Nakamura, T