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

• Rat models of 5′-AMP induced hypothermia and endotoxemia were established.
• 5′-AMP induced hypothermia improved the survival rate of endotoxemic rats.
• 5′-AMP induced hypothermia decreased the TLR4 expression in the lungs of endotoxemic rats
• 5′-AMP induced hypothermia inhibited the activation of the ERK1/2, p38, NF-κB and JNK pathways

Many studies have shown that LPS mainly activates four signal transduction pathways to induce inflammation, namely the p38, ERK1/2, JNK and IKK/NF-κB 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-κB in inflammatory rats. Our study concluded that AIH attenuated LPS-induced inflammation mainly by inhibiting activation on the ERK1/2, p38, JNK and NF-κB signaling pathways.