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.
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:Humancolonic 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.
Authors: R M Corcoran; P MacDonagh; F O'Connell; M E Morrissey; M R Dunne; R Argue; J O'Sullivan; D Kevans Journal: Dig Dis Sci Date: 2022-03-14 Impact factor: 3.199
Authors: Rodrigo B Mansur; Francheska Delgado-Peraza; Mehala Subramaniapillai; Yena Lee; Michelle Iacobucci; Flora Nasri; Nelson Rodrigues; Joshua D Rosenblat; Elisa Brietzke; Victoria E Cosgrove; Nicole E Kramer; Trisha Suppes; Charles L Raison; Andrea Fagiolini; Natalie Rasgon; Sahil Chawla; Carlos Nogueras-Ortiz; Dimitrios Kapogiannis; Roger S McIntyre Journal: J Psychiatr Res Date: 2020-12-04 Impact factor: 4.791