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

Int Immunopharmacol. 2014 Nov;23(1):205-10. doi: 10.1016/j.intimp.2014.09.002. Epub 2014 Sep 13.

Abstract

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 6h and 12h 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.

Keywords: Adenosine 5′-monophosphate; Endotoxemia; Hypothermia; Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / metabolism
  • Animals
  • C-Reactive Protein / metabolism
  • Chemokine CCL2 / blood
  • Disease Models, Animal
  • Endotoxemia / chemically induced
  • Endotoxemia / immunology*
  • Endotoxemia / therapy
  • Enzyme Activation
  • Humans
  • Hypothermia, Induced*
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharides / administration & dosage
  • MAP Kinase Signaling System
  • NF-kappa B / metabolism*
  • Rats
  • Rats, Wistar
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Chemokine CCL2
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • NF-kappa B
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Adenosine Monophosphate
  • C-Reactive Protein