NF-kappaB mediated transcriptional repression of acid modifying hormone gastrin.

NF-kappaB mediated transcriptional repression of acid modifying hormone gastrin.

Blog Article

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 Binoculars 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 JOOVA CREAM 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.