Involvement of Protein Kinase C delta in Iron Chelator-Induced IL-8 Production in Human Intestinal Epithelial Cells.
- Author:
Young Woo SOHN
1
;
Eun Young CHOI
;
Won Cheol HAN
;
Ki Jung YUN
;
Jae Min OH
;
Chang Duk JUN
Author Information
1. Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, Korea.
- Publication Type:Original Article
- Keywords:
Iron;
Intestinal epithelial cells;
IL-8;
PKCdelta
- MeSH:
Deferoxamine;
Epithelial Cells*;
HT29 Cells;
Humans*;
Interleukin-8*;
Iron;
Phosphorylation;
Protein Kinase C*;
Protein Kinase C-delta*;
Protein Kinases*;
RNA, Small Interfering;
Transfection
- From:Korean Journal of Anatomy
2005;38(1):21-30
- CountryRepublic of Korea
- Language:Korean
-
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.
