Functional modulation of Crohn's disease myofibroblasts by anti-tumor necrosis factor antibodies.

摘要: Background & Aims: Infliximab induces immune cell apoptosis by outside-to-inside signaling through transmembrane tumor necrosis factor- (mTNF). However, in inflamed gut, myofibroblasts also produce TNF-, and the affects of anti-TNF antibodies on these structural cells are unknown. We investigated action infliximab apoptosis, production matrix metalloproteinases (MMPs) tissue inhibitor (TIMP)-1, migration Crohn’s disease (CD) myofibroblasts. Methods: Colonic were isolated from patients with active CD controls. mTNF was evaluated Western blotting flow cytometry. Infliximab-treated analyzed for Annexin V staining caspase-3. TIMP-1 MMPs measured blotting, fibroblast assessed using an vitro wound-healing scratch assay. Results: showed higher expression than control had no effect myofibroblast caspase-3 activation, MMP-3 MMP-12. induced a significant dose-dependent increase production, which inhibited p38 mitogen-activated protein kinase SB 203580. The agents adalimumab, etanercept, p55 TNF-receptor‐human IgG fusion increased production. enhanced significantly recombinant human TIMP-1, infliximab-induced anti‐TIMP-1 neutralizing antibody. decreased collagen Conclusions: Our findings show novel therapeutic pathway therapies enhancing migration, may reduce MMP activity facilitate wound healing.