Involvement of protein kinase Cdelta in iron chelator-induced IL-8 production in human intestinal epithelial cells.
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 Gö6976, Gö6983, 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.
Choi
Eun-Young
EY
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
Lee
SungGa
S
Oh
Hyun-Mee
HM
Kim
Young-Dae
YD
Choi
Eun-Ju
EJ
Kim
Sang-Hyun
SH
Kim
Sang-Wook
SW
Choi
Suck-Chei
SC
Jun
Chang-Duk
CD
D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D016209:Interleukin-8; D007502:Iron Chelating Agents; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D007501:Iron; D051745:Protein Kinase C-delta