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.

Petito, V., Lopetuso, L. R., Arena, V., Stigliano, E., Boninsegna, A., Bibbò, S., Poscia, A., Alfieri, S., Rosa, F., Amato, A., Cammarota, G., Papa, A., Sgambato, A., Gasbarrini, A., Scaldaferri, F., Direct effect of infliximab on intestinal mucosa sustains mucosal healing: Exploring new mechanisms of action, <<DIGESTIVE AND LIVER DISEASE>>, 2016; 48 (4): 391-398. [doi:10.1016/j.dld.2015.12.008] [http://hdl.handle.net/10807/95046]

Direct effect of infliximab on intestinal mucosa sustains mucosal healing: Exploring new mechanisms of action

Petito, Valentina
Primo
;
Lopetuso, Loris Riccardo
Secondo
;
Arena, Vincenzo;Stigliano, Egidio;Bibbò, Stefano;Poscia, Andrea;Alfieri, Sergio;Rosa, Fausto;Amato, Arianna;Cammarota, Giovanni;Papa, Alfredo;Sgambato, Alessandro;Gasbarrini, Antonio
Penultimo
;
Scaldaferri, Franco
2016

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.
Inglese
Petito, V., Lopetuso, L. R., Arena, V., Stigliano, E., Boninsegna, A., Bibbò, S., Poscia, A., Alfieri, S., Rosa, F., Amato, A., Cammarota, G., Papa, A., Sgambato, A., Gasbarrini, A., Scaldaferri, F., Direct effect of infliximab on intestinal mucosa sustains mucosal healing: Exploring new mechanisms of action, <<DIGESTIVE AND LIVER DISEASE>>, 2016; 48 (4): 391-398. [doi:10.1016/j.dld.2015.12.008] [http://hdl.handle.net/10807/95046]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/95046
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