Effects of the RNA-binding protein, KSRP, on innate immune response against Helicobacter pylori infection in mice

Biochem Biophys Res Commun. 2018 Jan 8;495(2):1573-1579. doi: 10.1016/j.bbrc.2017.12.016. Epub 2017 Dec 6.

Abstract

Helicobacter pylori (H. pylori) contributes to various gastric diseases such as chronic gastritis, gastric ulcer, and gastric carcinoma. Host innate immune response against the pathogen plays a significant role in elimination of pathogen infection. Importantly, pathogen elimination is closely related to numerous inflammatory-related genes that participate in complex biological response of cells to harmful stimuli. Here we studied effects of the KH-type splicing regulatory protein (KSRP), a RNA-binding protein, on innate immune response against H. pylori infection. We found that H. pylori infection downregulated KSRP expression directly, and that KSRP overexpression repressed upregulation of CXCL-2 expression induced by H. pylori and facilitated H. pylori proliferation in vitro. Similarly, KSRP overexpression in H. pylori mice also facilitated H. pylori proliferation and colonization, and induced more severe gastric mucosal damage. Intriguingly, CXCL-2 and HMOX-1 were upregulated in H. pylori infected mice after KSRP overexpression. This difference in expression of these genes implicated that KSRP was closely associated with and directly participated in the innate immune response against H. pylori. These results were beneficial for understanding the in vivo function of KSRP on innate immune response against pathogen infection.

Keywords: Helicobacter pylori; Immune response; Infection; KSRP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chemokine CXCL2 / genetics
  • Down-Regulation
  • Female
  • Gastritis / genetics
  • Gastritis / immunology
  • Gastritis / pathology
  • Helicobacter Infections / genetics
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / pathology
  • Helicobacter pylori* / genetics
  • Helicobacter pylori* / immunology
  • Helicobacter pylori* / pathogenicity
  • Heme Oxygenase-1 / genetics
  • Humans
  • Immunity, Innate / genetics
  • Male
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / immunology*
  • Toll-Like Receptor 2 / genetics
  • Trans-Activators / genetics
  • Trans-Activators / immunology*
  • Up-Regulation

Substances

  • CXCL2 protein, human
  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • KHSRP protein, human
  • Khsrp protein, mouse
  • Membrane Proteins
  • RNA-Binding Proteins
  • TLR2 protein, human
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Trans-Activators
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Hmox1 protein, mouse