Yonsei Med J.  2015 May;56(3):862-866. 10.3349/ymj.2015.56.3.862.

Jak1/Stat3 Is an Upstream Signaling of NF-kappaB Activation in Helicobacter pylori-Induced IL-8 Production in Gastric Epithelial AGS Cells

Affiliations
  • 1Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea. kim626@yonsei.ac.kr
  • 2Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea.

Abstract

Helicobacter pylori (H. pylori) induces the activation of nuclear factor-kB (NF-kappaB) and cytokine expression in gastric epithelial cells. The Janus kinase/signal transducers and activators of transcription (Jak/Stat) cascade is the inflammatory signaling in various cells. The purpose of the present study is to determine whether H. pylori-induced activation of NF-kappaB and the expression of interleukin-8 (IL-8) are mediated by the activation of Jak1/Stat3 in gastric epithelial (AGS) cells. Thus, gastric epithelial AGS cells were infected with H. pylori in Korean isolates (HP99) at bacterium/cell ratio of 300:1, and the level of IL-8 in the medium was determined by enzyme-linked immonosorbent assay. Phospho-specific and total forms of Jak1/Stat3 and IkappaBalpha were assessed by Western blot analysis, and NF-kappaB activation was determined by electrophoretic mobility shift assay. The results showed that H. pylori induced the activation of Jak1/Stat3 and IL-8 production, which was inhibited by a Jak/Stat3 specific inhibitor AG490 in AGS cells in a dose-dependent manner. H. pylori-induced activation of NF-kappaB, determined by phosphorylation of IkappaBalpha and NF-kappaB-DNA binding activity, were inhibited by AG490. In conclusion, Jak1/Stat3 activation may mediate the activation of NF-kappaB and the expression of IL-8 in H. pylori-infected AGS cells. Inhibition of Jak1/Stat3 may be beneficial for the treatment of H. pylori-induced gastric inflammation, since the activation of NF-kappaB is inhibited and inflammatory cytokine expression is suppressed.

Keyword

Helicobacter pylori; Jak1/Stat3; IL-8; NF-kappaB; gastric epithelial cells

MeSH Terms

Blotting, Western
DNA, Bacterial/analysis/genetics
Epithelial Cells/metabolism
Gastric Mucosa/drug effects/*immunology/microbiology
Gene Expression Regulation/drug effects/*immunology
Gene Expression Regulation, Bacterial
Helicobacter Infections/immunology/*metabolism
Helicobacter pylori/genetics/pathogenicity/*physiology
Humans
Interleukin-8/genetics/*metabolism
Janus Kinase 1
NF-kappa B/biosynthesis/*metabolism
Phosphorylation
RNA, Messenger/metabolism
STAT3 Transcription Factor
Signal Transduction/genetics
DNA, Bacterial
Interleukin-8
Janus Kinase 1
NF-kappa B
RNA, Messenger
STAT3 Transcription Factor
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