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NF-kappaB Mediated Transcriptional Repression of Acid Modifying Hormone Gastrin

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Title NF-kappaB Mediated Transcriptional Repression of Acid Modifying Hormone Gastrin
 
Creator Datta De, Dipanjana
Datta, Arindam
Bhattacharjya, Sumana
Roychoudhury, Susanta
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description 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
 
Date 2013-08
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2436/1/PLOS_ONE.pdf
Datta De, Dipanjana and Datta, Arindam and Bhattacharjya, Sumana and Roychoudhury, Susanta (2013) NF-kappaB Mediated Transcriptional Repression of Acid Modifying Hormone Gastrin. PLOS ONE, 8 (8). e73409.
 
Relation http://dx.doi.org/10.1371/journal.pone.0073409
http://www.eprints.iicb.res.in/2436/