The Regulation Of TLR Signaling In Macrophages By Ca～(2+)/calmodium-dependent Protein Kinase Ⅱ

Various other signal pathways are involved in the tight regulation of TLR signaling. Here we investigated the potential role of CaMKII in TLR signaling in murine macrophages. We demonstrated that LPS (TLR4 agonist) could selectively and significantly induce activation of CaMKII in macrophages, while no significant CaMKII activation was detected in macrophages stimulated with CpG ODN (TLR9 agonist) or Poly I:C (TLR3 agonist). CaMKII inhibition by KN62, a specific CaMKII inhibitor, markedly decreased the production of IL-6 and TNF-α in LPS-inducedmacrophages and attenuated LPS-induced ERK, JNK, NFkB and IRF3 activation;however, CaMKII inhibition didn't affect the cytokine production and signaling pathways in macrophages induced by CpG ODN or Poly I:C. We found that CaMKII didn't affect the TLR4 expression and CaMKII may not interact with IRAKI, TAK1, TBK1, IKKe or TRAF6. It's assumed that CaMKII might selectively participate in TLR4 but not TLR3 and TLR9 signaling, and that it might be required for LPS-induced activation of macrophages. These findings provide evidence for the cross-talk between Ca²⁺/CaM/CaMKII and TLR signaling that leads to macrophage activation, which may facilitate the future investigation of the TLR signaling and its regulation.