title: Jak1/Stat3 is an upstream signaling of NF-κB activation in Helicobacter pylori-induced IL-8 production in gastric epithelial AGS cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Cha
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea.
authors.forename: Joo Weon
authors.initials: JW
authors.lastname: Lim
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.; Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea. kim626@yonsei.ac.kr.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism*; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D053613:Janus Kinase 1; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C507904:JAK1 protein, human; D053613:Janus Kinase 1
keywords: Helicobacter pylori; IL-8; Jak1/Stat3; NF-κB; gastric epithelial cells
references.citation: J Ginseng Res. 2014 Jan;38(1):8-15
references.pmid: 24558304
references.citation: BMJ. 1991 Jun 1;302(6788):1302-5
references.pmid: 2059685
references.citation: J Physiol Pharmacol. 2011 Apr;62(2):167-74
references.pmid: 21673364
references.citation: Mol Oncol. 2013 Jun;7(3):369-78
references.pmid: 23206899
references.citation: Helicobacter. 2014 Jun;19(3):194-201
references.pmid: 24612125
references.citation: Gut. 1992 Aug;33(8):1020-3
references.pmid: 1398224
references.citation: J Gastrointest Cancer. 2014 Jun;45(2):126-32
references.pmid: 24557546
references.citation: Nat Rev Cancer. 2009 Nov;9(11):798-809
references.pmid: 19851315
references.citation: Cell. 1994 Jan 28;76(2):253-62
references.pmid: 8293462
references.citation: J Physiol Pharmacol. 2009 Dec;60 Suppl 7:131-7
references.pmid: 20388956
references.citation: Bioessays. 1999 Jan;21(1):47-52
references.pmid: 10070253
references.citation: J Am Soc Nephrol. 2014 Aug;25(8):1737-48
references.pmid: 24578126
references.citation: Int Immunopharmacol. 2002 Oct;2(11):1509-20
references.pmid: 12433052
references.citation: Lab Invest. 2004 Jan;84(1):49-62
references.pmid: 14631383
references.citation: J Clin Invest. 2012 Apr;122(4):1553-66
references.pmid: 22378042
references.citation: J Biol Chem. 2002 Oct 25;277(43):40594-601
references.pmid: 12191995
references.citation: Inflamm Res. 2001 Sep;50(9):435-41
references.pmid: 11603847
references.citation: Cell. 1995 Jul 28;82(2):241-50
references.pmid: 7543024
references.citation: Nature. 2007 Oct 18;449(7164):862-6
references.pmid: 17943123
references.citation: Mol Cell Biol. 2005 Aug;25(15):6391-403
references.pmid: 16024778
references.citation: Biochem Pharmacol. 2006 Nov 30;72(11):1555-62
references.pmid: 16934228
references.citation: Dig Dis Sci. 2000 Mar;45(3):621-8
references.pmid: 10749342
references.citation: J Biol Chem. 2014 Jan 31;289(5):2687-700
references.pmid: 24337575
references.citation: JAKSTAT. 2013 Jan 1;2(1):e22925
references.pmid: 24058789
references.citation: Int J Biochem Cell Biol. 2010 Sep;42(9):1455-61
references.pmid: 20451655
references.citation: J Biol Chem. 2010 May 21;285(21):16042-50
references.pmid: 20348091
references.citation: J Ethnopharmacol. 2013 Nov 25;150(2):761-4
references.pmid: 24055641
references.citation: J Clin Pathol. 1995 Feb;48(2):133-6
references.pmid: 7745112
references.citation: Ann Intern Med. 1992 May 1;116(9):705-8
references.pmid: 1558340
references.citation: EMBO J. 2001 Jan 15;20(1-2):91-100
references.pmid: 11226159
references.citation: Pharmacology. 1999 Oct;59(4):201-11
references.pmid: 10474080
references.citation: Cell Signal. 2013 May;25(5):1166-75
references.pmid: 23357535
references.citation: JAMA. 1994 Jul 6;272(1):65-9
references.pmid: 8007082
references.citation: Dig Dis Sci. 2010 Apr;55(4):988-96
references.pmid: 19495976
references.citation: Nat Rev Immunol. 2003 Nov;3(11):900-11
references.pmid: 14668806
references.citation: J Clin Immunol. 2011 Feb;31(1):60-8
references.pmid: 20886283