Involvement of protein kinase Cdelta in iron chelator-induced IL-8 production in human intestinal epithelial cells.

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Choi EY, Lee S, Oh HM, Kim YD, Choi EJ, Kim SH, Kim SW, Choi SC, Jun CD

Involvement of protein kinase Cdelta in iron chelator-induced IL-8 production in human intestinal epithelial cells.

Life Sci. 2007 Jan 9;80(5):436-45. Epub 2006 Oct 14.

PubMed ID

17097691 [ View in PubMed

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Abstract

We have shown that the bacterial iron chelator, deferoxamine (DFO), triggers inflammatory signals, including the production of CXC chemokine IL-8, in human intestinal epithelial cells (IECs) by activating ERK1/2 and p38 kinase pathways. In the present study, we show that PKCdelta, one of the novel protein kinase C (PKC) isoforms, involves in signal transduction pathways leading to DFO-induced IL-8 production. Pretreatment of human intestinal epithelial HT-29 cells with rottlerin showed remarkable inhibition of DFO-induced IL-8 production. In contrast, other PKC inhibitors such as Go6976, Go6983, GF109203X, and staurosporine revealed less or no inhibitory effects on DFO-induced IL-8 production, suggesting a potential role of PKCdelta. Accordingly, DFO caused phosphorylation of PKCdelta in the Thr505 and Ser643 residues in HT-29 cells. Transfection of dominant-negative PKCdelta vector inhibited DFO-induced PKCdelta phosphorylation as well as IL-8 promoter activity. In addition, suppression of endogenous PKCdelta by siRNA significantly reduced DFO-induced IL-8 production. Collectively, these results suggest that PKCdelta plays a pivotal role in signaling pathways leading to iron chelator-induced IL-8 production in human IECs.