Direct effect of infliximab on intestinal mucosa sustains mucosal healing: exploring new mechanisms of action. Issue 4 (April 2016)

• Record Type: Journal Article
• Authors: Petito, Valentina; Lopetuso, Loris Riccardo; Arena, Vincenzo; Stigliano, Egidio; Boninsegna, Alma; Bibbò, Stefano; Poscia, Andrea; Alfieri, Sergio; Rosa, Fausto; Amato, Arianna; Cammarota, Giovanni; Papa, Alfredo; Sgambato, Alessandro; Gasbarrini, Antonio; Scaldaferri, Franco
• Is Part Of: Digestive and liver disease. Volume 48:Issue 4(2016)
• Page Start: 391
• Page End: 398
• Publication Date: 2016-04
• Subjects: Cellular proliferation -- Infliximab -- Mucosal healing -- TNF-α -- Wound repair; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2015.12.008
• Languages: English
• ISSNs: 1590-8658

Abstract

Abstract: Background: Infliximab is effective in inflammatory bowel disease through several mechanisms, possibly acting at the mucosal level. Aim: To assess the role of infliximab on intestinal mucosa and whether it contributes to mucosal healing. Methods: Human colonic mucosal biopsies were incubated with or without infliximab. Cultured biopsies were evaluated for histological staining, CD68, CD3, E-cadherin and phospho-extracellular signal-regulated kinases (ERK) expression, and apoptosis. A scratch assay and MTT assay were performed with Caco2 cells in the presence of infliximab and/or tumour necrosis factor (TNF)-α or treated with supernatants obtained from human peripheral blood mononuclear cells or human intestinal fibroblasts treated with TNF-α and infliximab alone or in association. Results: Infliximab-treated biopsies displayed a better histological appearance, reduced inflammation with an increase of E-cadherin, phospho-ERK and apoptosis. Supernatants showed lower TNF-α, IL-17, IL-6 and IL-8 concentration, with an increase in fibroblast-growth-factor. Motility at scratch assay and proliferation at MTT assay of Caco2 cells displayed differential modulation by TNF-α and infliximab, directly or through supernatants of human intestinal fibroblasts and human peripheral blood mononuclear cells exposed to them. Conclusion: Infliximab contributes to the mucosal healing process by acting directly at an intestinal mucosal level; infliximab indirectly affects epithelial cell migration and proliferation by acting on both fibroblasts and leukocytes.