Helicobacter pylori-elicited induction in gastric mucosal matrix metalloproteinase-9 (MMP-9) release involves

B L Slomiany1, A Slomiany2

  • 1Research Center, C875, Rutgers School of Dental Medicine, Rutgers, The State University of New Jersey, 110 Bergen Street, PO Box 1709, Newark, NJ, 07103-2400, USA. slomiabr@sdm.rutgers.edu.

Inflammopharmacology
|February 18, 2016
PubMed

Insights

Helicobacter pylori infection triggers matrix metalloproteinase-9 (MMP-9) release in the gastric mucosa. This study reveals a Rac1/MAPK cascade involving ERK and p38 pathways that drives MMP-9 release.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Cell Signaling

Background:

  • Matrix metalloproteinases (MMPs), particularly MMP-9, are implicated in inflammatory diseases like H. pylori-associated gastritis and ulcers.
  • H. pylori infection elevates MMP-9 production and activates mitogen-activated protein kinase (MAPK) and Rac1 signaling in gastric mucosa.

Purpose of the Study:

  • To investigate the role of the Rac1/MAPK pathway in the release of MMP-9 induced by H. pylori lipopolysaccharide (LPS).

Main Methods:

  • Investigated the involvement of MAPK (ERK, p38), Rac1, and cytosolic phospholipase A2 (cPLA2) in H. pylori LPS-induced MMP-9 release.
  • Examined the phosphorylation and membrane localization of cPLA2 and the translocation of p38.

Main Results:

  • H. pylori LPS induced MMP-9 release via MAPK, ERK, and p38 activation, involving Rac1 and cPLA2.
  • ERK-mediated cPLA2 phosphorylation at Ser(505) was crucial for its membrane localization with Rac1, requiring p38.
  • p38 activation and membrane translocation to the Rac1-GTP complex were vital for cPLA2-dependent MMP-9 release.

Conclusions:

  • The ERK/cPLA2 and Rac1/p38/cPLA2 signaling cascades are critical for H. pylori LPS-induced upregulation of gastric mucosal MMP-9 release.
  • This pathway provides a potential therapeutic target for H. pylori-associated gastric inflammation.

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