S100A8 Induces Secretion of MCP-1, IL-6, and IL-8 via TLR4 in Jurkat T Cells

In the pathogenesis of inflammatory diseases such as allergies, S100A8 acts as an important molecule and T lymphocytes are essential cytokine-releasing cells. In this study, we investigated the effect of S100A8 on release of cytokines, specifically MCP-1, IL-6, and IL-8 in T cells, and its associated signaling mechanism. S100A8 increased secretion of MCP-1, IL-6, and IL-8 in a time- and dose-dependent manner. Elevated secretion of MCP-1, IL-6, and IL-8 due to S100A8 was inhibited by the TLR4 inhibitor TLR4i, the PI3K inhibitor LY294002, the PKCδ inhibitor rottlerin, the ERK inhibitor PD98059, the p38 MAPK inhibitor SB202190, the JNK inhibitor SP600125, and the NF-κB inhibitor BAY-11-7085. S100A8 induced phosphorylation of ERK, p38 MAPK, and JNK in a time-dependent manner, and activation was suppressed by TLR4i, LY294002, and rottlerin. S100A8 induced NF-κB activation by Iκ-Bα degradation, and NF-κB activity was suppressed by PD98059, SB202190, and SP600125. These results indicate that S100A8 induces cytokine release via TLR4. Study of PI3K, PKCδ, MAPKs, and NF-κB will contribute to elucidation of the S100A8-invovled mechanism.