Involvement of Protein Kinase C delta in Iron Chelator-Induced IL-8 Production in Human Intestinal Epithelial Cells / 대한해부학회지

ABSTRACT

Our previous study demonstrated that a bacterial siderophore, deferoxamine (DFO), could trigger inflammatory signals in human intestinal epithelial cells as a single stimulus, leading to IL-8 production via ERK1/2 and p38 phosphorylation and NF-kappa B-independent mechanism. In the present study, we proved that a novel protein kinase C (PKC)isoform, PKCdelta, is necessary for DFO-induced IL-8 production. Pretreatment of HT-29 cells with rottlerin showed remarkable inhibition of DFO-induced IL-8 production. In contrast, a conventional PKC inhibitor Go6976 did not show significant inhibition of DFO-induced IL-8 production. DFO induced strong phosphorylation of PKCdelta in the epithelial cells. Overexpression of PKCdelta resulted in enhanced PKCdelta phosphorylation, while transfection with dominant-negative PKCdelta vector failed DFO-induced phosphorylation. In addition, transfection of HT-29 cells with siRNA targeting endogenous PKCdelta, which suppressed PKCdelta expression, attenuated DFO-induced IL-8 production. These results demonstrate that PKCdelta plays an important role in regulating iron chelator-induced IL-8 production in human intestinal epithelial cells.