A p55 TNF Receptor Immunoadhesin Prevents T Cell-Mediated Intestinal Injury by Inhibiting Matrix Metalloproteinase Production

摘要: Anti-TNF-alpha Ab therapy has been shown to be of benefit in the treatment active Crohn's disease, but tissue-injuring processes gut mediated by TNF-alpha that might inhibited neutralizing are unknown. In this work, we have used a p55 TNF receptor-human IgG fusion protein (TNFR-IgG) prevent severe mucosal injury ensues when lamina propria T cells explant cultures human fetal small intestine directly activated with lectin PWM. Following cell activation and associated injury, there is marked elevation soluble organ culture supernatants large increase mRNA transcripts. The addition TNFR-IgG at onset greatly reduced PWM-induced tissue without inhibiting IFN-gamma transcripts seen following activation. Mucosal model endogenously-produced matrix metalloproteinases (MMPs). When was added PWM-stimulated explants, reduction MMPs supernatants, especially stromelysin-1. Recombinant IL-1beta mesenchymal lines also caused an MMP production, only former TNFR-IgG. These results suggest one ways which causes stimulating secrete matrix-degrading metalloproteinases. Neutralization activity should help maintain integrity.