title: NF-kappaB mediated transcriptional repression of acid modifying hormone gastrin.
abstract: Helicobacter pylori is a major pathogen associated with the development of gastroduodenal diseases. It has been reported that H. pylori induced pro-inflammatory cytokine IL1B is one of the various modulators of acid secretion in the gut. Earlier we reported that IL1B-activated NFkB down-regulates gastrin, the major hormonal regulator of acid secretion. In this study, the probable pathway by which IL1B induces NFkB and affects gastrin expression has been elucidated. IL1B-treated AGS cells showed nine-fold activation of MyD88 followed by phosphorylation of TAK1 within 15 min of IL1B treatment. Furthermore, it was observed that activated TAK1 significantly up-regulates the NFkB subunits p50 and p65. Ectopic expression of NFkB p65 in AGS cells resulted in about nine-fold transcriptional repression of gastrin both in the presence and absence of IL1B. The S536A mutant of NFkB p65 is significantly less effective in repressing gastrin. These observations show that a functional NFkB p65 is important for IL1B-mediated repression of gastrin. ChIP assays revealed the presence of HDAC1 and NFkB p65 along with NCoR on the gastrin promoter. Thus, the study provides mechanistic insight into the IL1B-mediated gastrin repression via NFkB.
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Dipanjana
authors.initials: D
authors.lastname: Datta De
authors.forename: Arindam
authors.initials: A
authors.lastname: Datta
authors.forename: Sumana
authors.initials: S
authors.lastname: Bhattacharjya
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
mesh_terms: D002460:Cell Line; D056970:Co-Repressor Proteins / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005755:Gastrins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D056970:Co-Repressor Proteins; D050881:E1A-Associated p300 Protein; D005755:Gastrins; D056284:Histone Deacetylase 1; D053583:Interleukin-1beta; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D051996:Transcription Factor RelA; D000099151:MAP Kinase Kinase Kinase 7; C494360:EP300 protein, human