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Visit our Expo - Redox and Inflammation signaling 2012

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Crosstalk between NF-kB <strong>and</strong> AP-1 in Helicobacter pylori-mediated inflammation in<br />

human gastric epithelial cells<br />

Hyeyoung Kim<br />

Department of Pharmacology <strong>and</strong> Brain Korea 21 Project for Medical Science, Yonsei<br />

University College of Medicine, Seoul 120-752, Korea. Email:<br />

kim626@yumc.yonsei.ac.kr<br />

Previously we have shown that inflammatory enzymes such as cyclooxygenase-2 (COX-2)<br />

<strong>and</strong> inducible nitric oxide syntahse (iNOS) were expressed in H. pylori-infected gastric<br />

epithelial cells. The expression of COX-2 <strong>and</strong> iNOS may be regulated by NF-kB <strong>and</strong> AP-1.<br />

Present study aims to investigate whether H. pylori-induced expressions of COX-2 <strong>and</strong> iNOS<br />

are regulated by NF-kB <strong>and</strong> AP-1 in gastric epithelial AGS cells, <strong>and</strong> whether the<br />

transcriptional regulation of COX-2 or iNOS is inhibited by transfection of antisense<br />

oligodeoxynucleotide (AS ODN) for NF-kB subunit p50 or c-jun dominant negative mutant<br />

gene (TAM-67). As a result, H. pylori induced the expression of COX-2 <strong>and</strong> iNOS via<br />

activation of NF-kB <strong>and</strong> AP-1, which was inhibited in the cells transfected with either p50 AS<br />

ODN or TAM-67. The activated NF-kB complex was p65/p50 hetero- <strong>and</strong> p50/p50 homo-<br />

dimmers while the activated AP-1 complex was a c-jun/c-fos heterodimer in H. pyloriinfected<br />

AGS cells. In conclusion, NF-kB <strong>and</strong> AP-1 share H. pylori-mediated inflammation<br />

<strong>signaling</strong> by inducing COX-2 <strong>and</strong> iNOS expression in gastric epithelial cells. Either<br />

suppression of NF-kB or AP-1 may inhibit H. pylori-induced inflammation in gastric<br />

epithelial cells.<br />

Publication list (2002-2005)<br />

1) NADPH oxidase <strong>and</strong> apoptosis in cerulein-stimulated pancreatic acinar cells. JH Yu, JW<br />

Lim, KH Kim, T Morio, H Kim. Free Rad Biol Med 39: 590-602, 2005<br />

2) NADPH oxidase mediates interleukin-6 expression in cerulein-stimulated pancreatic acinar<br />

cells. JH Yu, JW Lim, H Kim, KH Kim, Int J Biochem Cell Biol 37:1458-1469, 2005<br />

3) Cellular stress - related protein expression in Helicobacter pylori - infected gastric<br />

epithelial AGS cells. JW Lim, H Kim, JM Kim, JS Kim, HC Jung, KH Kim, Int J Biochem<br />

Cell Biol 36:1624-1634, 2004.<br />

4) Oxidative stress - related proteome changes in Helicobacter pylori - infected human gastric<br />

mucosa. HY Baek, JW Lim, H Kim, JM Kim, JS Kim, HC Jung, KH Kim, Biochem J<br />

379:291-299, 2004<br />

5) Helicobacter pylori in a Korean isolate activates mitogen-activated protein kinases, AP-1,<br />

<strong>and</strong> NF-!B <strong>and</strong> induces chemokine expression in gastric epithelial AGS cells. JH Seo, JW<br />

Lim, H Kim, KH Kim, Lab Inv 84:49-62, 2004<br />

6) The Ku antigen-recombination signal-binding protein J! complex binds to the nuclear<br />

factor-!B p50 promoter <strong>and</strong> acts as a positive regulator of p50 expression in human gastric<br />

cancer cells. JW Lim, H Kim, KH Kim, J Biol Chem 279(1):231-237, 2004<br />

7) Role of oxygen free radicals in patients with acute pancreatitis. BK Park, JB Chung, JH<br />

Lee, JH Suh, SW Park, SY Song, H Kim, KH Kim, JK Kang, World J Gastroenterology<br />

9(10):2266-2269, 2003<br />

8) Oxidative stress induces nuclear loss of DNA repair proteins Ku70 <strong>and</strong> Ku80 <strong>and</strong> apoptosis<br />

in pancreatic acinar AR42J cells. JY Song, JW Lim, H Kim, T Morio, KH Kim.. J Biol Chem<br />

278 (38):36676-36687, 2003 Oct.<br />

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