Role of tumor necrosis factor receptors in an animal model of acute colitis.
TNF-alpha is known to play an important role in inflammatory bowel disease (IBD); however, the pathophysiological role of its receptors is still under study. Acute colitis was induced in rats by intracolonic administration of trinitrobenzene sulfonic acid (TNBS). Control rats received the ethanol vehicle. Rats were sacrificed 72 h later and samples of tissue and fluids were collected. There was a significant increase in the protein levels of sTNF-alpha, sTNFRI, and sTNFRII in the peritoneal fluid (PF) of experimental rats. TNF-alpha, TNFRI, and TNFRII mRNA expression was increased significantly in the colon of experimental animals compared to controls. TRAF3 and TRAF5 expression was also significantly higher, as was that of the adhesion molecules ICAM-1 and E-selectin. The increased expression of TNF-alpha, TNFRs, and the associated signaling factors in the colon of this rat model of IBD provides further evidence for their involvement in the promotion of inflammation and tissue damage. In addition, increased levels of sTNFRs in the PF of experimental rats--particularly sTNFRII--may be involved in the development of colitis by serving as a reservoir of TNF-alpha, and thus provide a novel therapeutic target for IBD.
Rojas-Cartagena
Carmencita
C
Department of Microbiology, Ponce School of Medicine, Ponce, PR 00732-7004, USA.
Flores
Idhaliz
I
Appleyard
Caroline B
CB
D000208:Acute Disease; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007421:Intestine, Small / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D019040:E-Selectin; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D014302:Trinitrobenzenesulfonic Acid