シクロスポリンAによる樹状細胞のIL-12分泌誘導作用

概要

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IL-12 secretion from dendritic cells (DCs) is essential for Th1 development and cytotoxic T cell (CTL) activation. A recent study showed that inhibition of CD40 ligand (CD40L)-induced IL-12 secretion was associated with calcium signaling. However, the precise inhibitory mechanism remains unclear. In order to clarify this mechanism, we examined the effect of a calcineurin (calcium-calmodulin dependent serine/threonine phosphatase) inhibitor, cyclosporin A (CyA) on phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) which is a kind of serine/threonine kinase and essential for IL-12 production on CD40 signaling cascades in human monocyte-derived immature DCs. We demonstrated that CyA could induce p38 MAPK phosphorylation and IL-12 production, and that CyA-induced p38 MAPK phosphorylation was cancelled by A23187. These results suggest that CyA enhances p38MAPK phosphorylation by inhibiting calcineurin phosphatase activity. CyA has been used as an immunosuppressive agent, which inhibits T cell proliferation. However, concerning these pharmacological actions, it is likely that this drug enhances Th1 development and cytotoxic T cell (CTL) activation.
新潟大学の論文
2006-01-10