| 저자(한글) |
Nam, A Reum,Kim, Da Hae,Kim, Mun Jeong,Lee, Ji-Sook,Yang, Seung-Ju,Kim, In Sik |
| 초록 |
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 $PKC{ delta}$ inhibitor rottlerin, the ERK inhibitor PD98059, the p38 MAPK inhibitor SB202190, the JNK inhibitor SP600125, and the NF- ${ kappa}B$ 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- ${ kappa}B$ activation by $I{ kappa}-B{ alpha}$ degradation, and NF- ${ kappa}B$ activity was suppressed by PD98059, SB202190, and SP600125. These results indicate that S100A8 induces cytokine release via TLR4. Study of PI3K, $PKC{ delta}$ , MAPKs, and NF- ${ kappa}B$ will contribute to elucidation of the S100A8-invovled mechanism. |
