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

HMGB1-RAGE signaling pathway is involved in the development of ALI/ARDS. At the same time, activation of PPAR gamma has been shown to inhibit the occurrence of ALI/ARDS. However, it is unknown whether activation of PPAR gamma 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 ALL in mice; these were accompanied with elevated expression of HMGB1 and RAGE. Prior treatment of mice with PPAR gamma 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 ALL This study suggests that activation of PPAR gamma 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. (C) 2014 Elsevier B.V. All rights reserved.