Stabilization of IFN-γ mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells
Stabilization of IFN-γ mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells
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DOI：
10.1182/blood-2004-07-2782
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发表时间：
2005-01-01
期刊：
影响因子：
20.3
通讯作者：
Clark, AR
中科院分区：
文献类型：
--
作者：
Mavropoulos, A;Sully, G;Clark, AR
The rapid induction of interferon-gamma (IFN-gamma) by innate cytokines such as interleukin 12 (IL-12) and IL-18 is critical for immunity against infectious pathogens. We investigated the molecular mechanisms underlying this response. IL-12 and IL-18 rapidly and synergistically induced the secretion of IFN-gamma by freshly purified human peripheral blood lymphocytes. At early time points, IFN-gamma was expressed almost exclusively by natural killer cells and in both CD56(bright) and CD56(dim) subpopulations. Mitogen-activated protein kinase p38 was activated strongly by IL-18 and weakly by IL-12 in natural killer cells but was not activated by either cytokine in T cells. The expression of IFN-gamma mRNA and protein was dose-dependently blocked by SB203580, a specific inhibitor of mitogen-activated protein kinase p38, which also caused a dramatic destabilization of IFN-gamma mRNA. The 3' untranslated region (UTR) of IFN-gamma mRNA conferred p38 responsiveness to a heterologous reporter mRNA. Therefore, the synergistic induction of IFN-gamma by IL-12 and IL-18 in natural killer cells is mediated at least in part by p38-dependent and 3'UTR-mediated stabilization of IFN-gamma mRNA. (C) 2005 by The American Society of Hematology.
