Involvement of the Mannose Receptor and p38 Mitogen-Activated Protein Kinase Signaling Pathway of the Microdomain of the Integral Membrane Protein after Enteropathogenic Escherichia coli Infection

Abstract

The microdomain of the integral membrane protein (MIMP) has been shown to adhere to mucin and to antagonize the adhesion of enteropathogenic Escherichia coli (EPEC) to epithelial cells; however, the mechanism has not been fully elucidated. In this study, we further identified the receptor of MIMP on NCM460 cells and investigated the mechanism (the p38 mitogen-activated protein kinase [MAPK] pathway) following the interaction of MIMP and its corresponding receptor, mannose receptor. We first identified the target receptor of MIMP on the surfaces of NCM460 cells using immunoprecipitation-mass spectrometry technology. We also verified the mannose receptor and examined the degradation and activation of the p38 MAPK signaling pathway. The results indicated that MIMP adhered to NCM460 cells by binding to the mannose receptor and inhibited the phosphorylation of p38 MAPK stimulated after EPEC infection via inhibition of the Toll-like receptor 5 pathway. These findings indicated that MIMPs relieve the injury of NCM460 cells after enteropathogenic E. coli infection through the mannose receptor and inhibition of the p38 MAPK signaling pathway, both of which may therefore be potential therapeutic targets for intestinal diseases, such as inflammatory bowel disease.

Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction

“…After three lists were generated by the three computational programs, a fourth list, which contained genes predicted by all the three initial computational programs (Table 3), was generated from the analysis of bioinformatics with the MetaCoreTM platform. The MAPK signal pathway was selected as the target molecular signal for further analysis because our previous study indicated p38 MAPK to be involved in the regulation of intestinal permeability and the intestinal barrier function [18]. Therefore, we investigated the interaction of let-7b with p38 MAPK.…”

“…The target gene was predicted using three different computational programs, TargetScan, PicTar, and miRanda. Through bioinformatics analysis using the MetaCoreTM platform, p38 MAPK was selected as the target, which was reported previously as a positive regulator during intestinal barrier dysfunction [1, 18]. Dual-luciferase reporter assay indicated the p38 MAPK as a target of let-7b.…”

“…The result where in the phosphorylated JNK was increased in let-7b IKO mice further verified that MAPK pathway maybe involved in the intestinal inflammation response of let-7b IKO mice. Elevated cytokines induced MAPK activation, which evoked the intestinal inflammation response [18]. The let-7b-mediated crosstalk between IRS-2/ Akt and MAPK is involved in oral squamous cell carcinoma by targeting insulin-like growth factor [24].…”

“…The membrane was washed thrice (60 min each time) with TBS-T buffer and developed using the enhanced chemiluminescence method (ECL kit; Pierce, Illinois) according to the manufacturer’s instructions [18]. …”

Involvement of PKA signalling in anti‐inflammatory effects of chitosan oligosaccharides in IPEC‐J2 porcine epithelial cells

“…Results were expressed as mean ± SE (n = 6). Mannose receptor is a C-type lectin which can recognize oligosaccharides terminating in mannose, fucose or N-acetyl glucosamine and has been found in intestinal epithelium cells (Liu et al, 2012;Taylor et al, 2005). Moreover, mannose receptor is associated with internalization of ligands and a signal transduction pathway leading to cytokine production (Stahl & Ezekowitz, 1998;Tan et al, 1997).…”