Cordycepin inhibits LPS-induced inflammatory responses by modulating NOD-Like Receptor Protein 3 inflammasome...

The aim of this study is to examine the effects of cordycepin (CRD) on LPS-induced inflammatory response in macrophages and further investigate the underlying molecular mechanisms.

Cultured mouse RAW264.7 macrophages and human THP-1-derived macrophages were used in this study. The mRNA and protein expression levels of cytokine IL-1β, IL-6, TNF-α, and MCP-1 were detected by real time RT-PCR, ELISA and Western blot, respectively. The activation of NOD-Like Receptor Protein 3 (NLRP3) inflammasome was analyzed with Western blot analysis and immunofluorescence staining. The ERK1/2 activation was assessed by Western blot analysis.

The results demonstrated that pretreatment with CRD (6.25, 12.5, 25, 50μmol/L) dose-dependently inhibited LPS-induced expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1) and cyclooxygenase 2 (COX-2) in mouse RAW264.7 cells. Similar results were obtained in human THP-1-derived macrophages with CRD. Furthermore, CRD remarkably inhibited LPS-induced activation of the NLRP3 inflammasome and ERK1/2 signaling pathway in RAW264.7 cells.

CRD exerts anti-inflammatory effects in LPS-induced murine and human macrophages at least in part by inhibiting the activation of NLRP3 inflammasome and ERK1/2 signaling pathway as well as inhibition of COX2-mediated inflammatory response.