Activation of PPAR纬 attenuates LPS-induced acute lung injury by inhibition of HMGB1-RAGE levels

详细信息    查看全文

• 作者：Guizuo Wang ; Lu Liu ; Yonghong Zhang ; Dong Han ; Jiamei Lu ; Jing Xu ; Xinming Xie ; Yuanyuan Wu ; Dexin Zhang ; Rui Ke ; Shaojun Li ; Yanting Zhu ; Wei Feng ; Manxiang Li ; ^{manxiangli@hotmail.com" class="auth_mail}
• 关键词：PPAR纬 ; HMGB1 ; RAGE ; ALI
• 刊名：European Journal of Pharmacology
• 出版年：5 March, 2014
• 年：2014
• 卷：726
• 期：Complete
• 页码：27-32
• 全文大小：1865 K

文摘

HMGB1-RAGE signaling pathway is involved in the development of ALI/ARDS. At the same time, activation of PPAR纬 has been shown to inhibit the occurrence of ALI/ARDS. However, it is unknown whether activation of PPAR纬 benefits ALI/ARDS by regulation of HMGB1-RAGE signaling. This study aims to address these issues. We found in this study that LPS induced dramatic pathological changes of ALI in mice; these were accompanied with elevated expression of HMGB1 and RAGE. Prior treatment of mice with PPAR纬 agonist rosiglitazone significantly suppressed LPS-induced ALI and reversed the elevation of HMGB1 and RAGE; these were accompanied with the induction of HO-1. The presence of selective HO-1 inhibitor Znpp abolished the protective effects of rosiglitazone on LPS-induced ALI. This study suggests that activation of PPAR纬 inhibits the development of LPS-induced ALI by negative modulation of HMGB1-RAGE pathway, and has a potential value in the clinical treatment of such conditions.