Elevating calcium in Th2 cells activates multiple pathways to induce IL-4 transcription and mRNA stabilization

被引：33

作者：

Guo, Liying ^{[1
]}

Urban, Joseph F. ^{[2
]}

Zhu, Jinfang ^{[1
]}

Paul, William E. ^{[1
]}

机构：

[1] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA

[2] USDA ARS, Nutrient Requirements & Funct Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA

来源：

JOURNAL OF IMMUNOLOGY | 2008年 / 181卷 / 06期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.4049/jimmunol.181.6.3984

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

PMA and ionomycin cause T cell cytokine production. We report that ionomycin alone induces IL-4 and IFN-gamma, but not IL-2, from in vivo- and in vitro-generated murine Th2 and Th1 cells. Ionomycin-induced cytokine production requires NFAT, p38, and calmodulin-dependent kinase IV (CaMKIV). Ionomycin induces p38 phosphorylation through a calcium-dependent, cyclosporine A-inhibitable pathway. Knocking down ASK1 inhibits ionomycin-induced p38 phosphorylation and IL-4 production. lonomycin also activates CaMKIV, which, together with p38, induces AP-1. Cooperation between AP-1 and NFAT leads to 114 gene transcription. p38 also regulates IL-4 production by mRNA stabilization. TCR stimulation also phosphorylates p38, partially through the calcium-dependent pathway; activated p38 is required for optimal IL-4 and IFN-gamma.

引用

页码：3984 / 3993

页数：10

共 50 条

[1] Defective signaling in a subpopulation of CD4+ T cells in the absence of Ca2+/calmodulin-dependent protein kinase IV [J].