Attenuation of interferon-gamma mRNA expression in activated Jurkat T cells by exogenous zinc via down-regulation of the calcium-independent PKC-AP-1 signaling pathway

作者：Hayashi Kumiko^*; Ishizuka Satoshi; Yokoyama Chieko; Hatae Toshihisa

来源：Life Sciences, 2008, 83(1-2): 6-11.

DOI：10.1016/j.lfs.2008.04.022

• zinc
• interferon-gamma
• AP-1
• NFAT
• T cell activation
• PKC-theta
• anti-inflammatory effect

Zinc is known to modulate a wide variety of cellular functions including anti-inflammatory responses. We examined the intracellular signaling pathways that contribute to the regulation of interferon-gamma (IFN-gamma) by zinc in activated human Jurkat T cells. Zinc significantly reduced IFN-gamma expression and activator protein-1 (AP-1) signaling in cells activated by phorbol 12-myristate 13-acetate (PMA) and phytohemagglutinin (PHA) without affecting cell viability. Moreover, partial inhibition of AP-1 activity by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, resulted in marked reduction of IFN-gamma transcription. We also found that this inhibitory effect of zinc on AP-1 signaling was abolished by treatment with rottlerin, a selective inhibitor of calcium-independent protein kinase C (PKC). These results suggest a novel target of zinc in the calcium-independent protein kinase C-AP-1 pathway to regulate endogenous IFN-gamma gene expression in activated T cells.

• 出版日期2008-7-4