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.
Nakai
Minoru
M
Department of Internal Medicine, Gifu University Graduate School of Medicine, Japan.
Sudo
Kaori
K
Yamada
Yasuhiro
Y
Kojima
Yasushi
Y
Kato
Tomohiro
T
Saito
Kuniaki
K
Moriwaki
Hisataka
H
Seishima
Mitsuru
M
D000818:Animals; D017209:Apoptosis; D003092:Colitis / Q000139:chemically induced* / Q000276:immunology* / Q000662:veterinary; D005260:Female; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology* / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid