Anti-TNF-α mAb protects intestinal mucosal barrier integrity in the patients of Crohn’s disease via P38 MAPK/NF-κB p65-mediated expression of tight junction proteins

Abstract Objective To explore the potential mechanism of anti-TNF mAb therapy in protecting mucosal barrier integrity in the patients of Crohn's disease. Methods 382 patients with active Crohn's disease from January 2018 to October 2019 were recruited and treated with anti-TNF mAb therapy at the week 0,2,6, then every 8 weeks. The general clinical data were evaluated at the 14 th week and the intestinal mucosa was harvested to determine the expression of tight junction proteins.The Caco-2 and HT-19 cell lines were cultured and divided into normal control group, LPS injury group, IFX intervention + LPS injury group. The supernatant and total protein were collected to test the level of pro-inflammatory cytokines and tight junction proteins. Results Anti-TNF mAb therapy effectively increased the level of hemoglobin (Hb), BMI and the expression of intestinal epithelial tight junction proteins (occludin, claudin-1, jam-a and zo-1) in the patients of Crohn's disease, and decreased the release of c-reactive protein (CRP), pro-inflammatory cytokines (TNF-α , IFN-γ , IL-2, IL-6, IL-8 and IL-17a) and CDAI scores. Phosphorylation of P38 MAPK and NF-κB p65 were increased significantly in untreated patients of Crohn's disease, while Anti-TNF-α mAb decreased the phosphorylation ratio. At the same time, we also carried out relevant studies in vitro. Conclusion Anti-TNF-α mAb therapy effectively induces clinical remission of active patients of Crohn's disease, reduces the intestinal inflammatory infiltration, decreases the release of inflammatory cytokines, and maintains mucosal barrier integrity through the p38 MAPK/NF-κB p65 pathway.