Roles of mPGES-1, an inducible prostaglandin E synthase, in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model

详细信息    查看全文

• 作者：Hiromi Matsuda^a ; ^b ; ^c ; Kanako Hosono^a ; ^c ; Seri Tsuru^a ; ^b ; ^c ; Chie Kurashige^a ; ^b ; ^c ; Kazuki Sekiguchi^a ; ^c ; Shizuo Akira^d ; Satoshi Uematsu^e ; Hirotsugu Okamoto^b ; Masataka Majima^a ; ^c ; ^{mmajima@med.kitasato-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Lymphangiogenesis ; Inflammation ; Prostaglandin ; Synthase ; Cyclooxygenase-2 ; mPGES-1 ; Peritonitis
• 刊名：Life Sciences
• 出版年：2015
• 出版时间：1 December 2015
• 年：2015
• 卷：142
• 期：Complete
• 页码：1-7
• 全文大小：1592 K

文摘

Lymphangiogenesis is frequently observed during inflammation, and this inflammation-induced lymphangiogenesis (IL) is a phenomenon actively involved in the pathophysiology of inflammation. We explored the roles of an inducible prostaglandin E synthase, mPGES-1, in IL elicited by lipopolysaccharide (LPS).

Main methods

Peritonitis was induced in mice by intraperitoneal injection of LPS (E. coli 0111-B4; 25 μg/mouse every 2 days), and IL was evaluated by LYVE-1 immunostaining of whole-mount diaphragm tissues.

Key findings

Compared to vehicle-treated wild-type (WT) mice, lymphatics in the diaphragms of mice injected with LPS were widened and the number of LYVE-1-positive ladder-structured lymphatics increased temporally. This increase in lymphangiogenesis was accompanied by increased expression of vascular endothelial growth factor (VEGF)-C/D in the diaphragms. In mice treated with celecoxib, a cyclooxygenase-2 inhibitor, IL was suppressed with reduced expression of VEGF-C/D. This was also observed in mPGES-1 knockout mice (KO). Immunoreactive COX-2 and mPGES-1 were detected in both CD11b-positive and CD3ε-positivecells in the diaphragm. When FITC–dextran was injected into the peritoneal cavities, the amount of residual FITC–dextran was reduced significantly in WT mice injected with LPS, and this reduction was significantly decreased in mPGES-1 KO mice.

Significance

The present results suggest that mPGES-1 plays a significant role in lymphangiogenesis during inflammation, and represents a novel target for controlling IL.