Regulation Of TLR4 Signaling In Macrophages By Death-resistant Protein DRP

We report here the roles of DRP in TLR4 signaling in macrophages. Our study has demonstrated that DRP can regulate LPS-activated TLR4 signaling pathway in macrophages by inhibiting the production of LPS-induced proinflammatory cytokines but enhancing the production of IFN-6. We also found that DRP overexpression increased the level of phosphorylated ERK and JNK, enhanced the LPS-induced phosphorylation of 1κBa and inhibited the LPS-induced transcription activity of NF-kB. Higher level of IRF3 phosphorylation and nuclear localization of IRF3 were also observed in DRP-overexpressing macrophages. The data of DRP-silencing were opposite to these. Therefore, based on our studies, we suggest that DRP can promote the TLR4 signal transduction toward MyD88-independent pathway but inhibit the activation of MyD88-dependent pathway. Therefore, DRP may function as a switchmolecule in TLR4 signal transduction and determine the activation pathways.