Adenosine 5′-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats

Many studies have shown that LPS mainly activates four signal transduction pathways to induce inflammation, namely the p38, ERK1/2, JNK and IKK/NF-kappa B pathways. Studies have demonstrated that 5'-AMP-induced hypothermia (AIH) exhibits high anti-inflammatory capabilities. In this study, we explore that how AIH inhibits the inflammatory response. Wistar rats were divided into five groups: a control group, an LPS group, a 5'-AMP pre-treatment group, a 5'-AMP post-treatment group and a 5'-AMP group. For each group, plasma and lung were collected from the rats at 6 h and 12 h after LPS injection. ELISA assays were used to detect plasma levels of CD14, CRP and MCP-1. Inflammatory pathway activation and TLR4 expression were assayed separately by Western blot analysis and immunohistochemistry. Our results showed that rats treated with AIH either before or after an LPS-challenge had a significant decrease in plasma levels of CD14, CRP and TLR4 compared with rats that received LPS only. Western blot analysis showed that AIH inhibited the activation of extracellular signal-regulated kinases (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) and NF-kappa B in inflammatory rats. Our study concluded that AIH attenuated LPS-induced inflammation mainly by inhibiting activation on the ERK1/2, p38, JNK and NF-kappa B signaling pathways. (C) 2014 Elsevier B.V. All rights reserved.