Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 6, Pages 3984-3993Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.6.3984
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- Intramural Research Program of the National Institutes of Health
- National Institute of Allergy and Infections Diseases
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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.
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