TY - JOUR
T1 - Direct effect of infliximab on intestinal mucosa sustains mucosal healing: Exploring new mechanisms of action
AU - Petito, Valentina
AU - Lopetuso, Loris Riccardo
AU - Arena, Vincenzo
AU - Stigliano, Egidio
AU - Boninsegna, Alma
AU - Bibbò, Stefano
AU - Poscia, Andrea
AU - Alfieri, Sergio
AU - Rosa, Fausto
AU - Amato, Arianna
AU - Cammarota, Giovanni
AU - Papa, Alfredo
AU - Sgambato, Alessandro
AU - Gasbarrini, Antonio
AU - Scaldaferri, Franco
PY - 2016
Y1 - 2016
N2 - 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)-alpha or treated with supernatants obtained from human peripheral blood mononuclear cells or human intestinal fibroblasts treated with TNF-alpha 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-alpha, 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-alpha 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. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
AB - 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)-alpha or treated with supernatants obtained from human peripheral blood mononuclear cells or human intestinal fibroblasts treated with TNF-alpha 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-alpha, 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-alpha 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. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
KW - Cellular proliferation
KW - Infliximab
KW - Mucosal healing
KW - TNF-α
KW - Wound repair
KW - Cellular proliferation
KW - Infliximab
KW - Mucosal healing
KW - TNF-α
KW - Wound repair
UR - http://hdl.handle.net/10807/248954
U2 - 10.1016/j.dld.2015.12.008
DO - 10.1016/j.dld.2015.12.008
M3 - Article
SN - 1590-8658
VL - 48
SP - 391
EP - 398
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
ER -
