The role of the tumor necrosis factor receptor in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice.

We investigated the effect of TNBS administration using TNF-receptor knockout mice to elucidate the role of TNF receptors in chronic inflammation of the colon. Histologically, inflammatory cell scores showed no significant differences among TNBS-administered groups, while tissue damage scores were significantly lower in TNFR-1KO and TNFR-1,2KO than in WT. The apoptotic indexes of lamina propria mononuclear cells (LPMC) of all TNBS-administered groups were significantly lower than that of controls. TNF-alpha mRNA expression in the colon was significantly higher in all TNBS-administered groups than in controls. And NF-kappa B activities were enhanced in WT and TNFR-2KO compared with controls. Our data indicate that the TNF/TNFR-1 signaling system mediates mucosal damage through the enhancement of NF-kappa B activity and that continuous infiltration of TNF-producing cells, probably a key pathogeneses of colitis, may be closely associated with defective apoptosis of LPMC, which is possibly independent of the TNF/TNFR signaling system in TNBS-induced colitis.