Jak1/Stat3 is an upstream signaling of NF-κB activation in Helicobacter pylori-induced IL-8 production in gastric epithelial AGS cells

• Published in: Yonsei medical journal 2015, 56(3), , pp.862-866
• Main Authors: Cha, Boram, Lim, Joo Weon, Kim, Hyeyoung
• Format: Article
• Language: English
• Subjects: Blotting, Western; Brief Communication; DNA, Bacterial - analysis; DNA, Bacterial - genetics; Epithelial Cells - metabolism; Gastric Mucosa - drug effects; Gastric Mucosa - immunology; Gastric Mucosa - microbiology; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Gene Expression Regulation, Bacterial; Helicobacter Infections - immunology; Helicobacter Infections - metabolism; Helicobacter pylori - genetics; Helicobacter pylori - pathogenicity; Helicobacter pylori - physiology; Humans; Interleukin-8 - genetics; Interleukin-8 - metabolism; Janus Kinase 1; NF-kappa B - biosynthesis; NF-kappa B - metabolism; Phosphorylation; RNA, Messenger - metabolism; Signal Transduction - genetics; STAT3 Transcription Factor; 의학일반
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2015.56.3.862

Helicobacter pylori (H. pylori) induces the activation of nuclear factor-kB (NF-κB) 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-κB 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 IκBα were assessed by Western blot analysis, and NF-κB 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-κB, determined by phosphorylation of IκBα and NF-κB-DNA binding activity, were inhibited by AG490. In conclusion, Jak1/Stat3 activation may mediate the activation of NF-κB 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-κB is inhibited and inflammatory cytokine expression is suppressed.