title: Blocking TNF-α by combination of TNF-α- and TNFR-binding cyclic peptide ameliorates the severity of TNBS-induced colitis in rats.
abstract: Tumor necrosis factor alpha (TNF-α) has been implicated in the pathogenesis of Crohn's disease. TNF antagonists are effectively used to treat these patients, although the efficiency of different antagonists varies. In the present study we combined TNF-α binding cyclic peptide (TBCP) and TNFR1 binding cyclic peptide (TRBCP) to treat TNBS-induced colitis in rats for one week. The symptoms of colitis including bloody diarrhea, rectal prolapse, and a profound and sustained weight loss were significantly ameliorated and the colon inflammatory damage, both macroscopic and histological scores, MPO activity, and NO production were markedly decreased in rats by neutralization of TNF-α and blocking TNFR1, as compared with those in rats treated with irrelevant peptide or normal saline (P<0.05). The transcripts of IL-1β and IL-8, and the protein expression of TNF-α in rats treated with both TBCP and TRBCP were also down-regulated (P<0.05), while these proinflammatory cytokines remained unchanged in rats treated with irrelevant peptide or normal saline. These findings suggest that the combination of TNF-α- and TNFR1-binding peptide effectively improves the symptoms of TNBS-induced colitis and alleviates colonic pathological damages in rats. This combination may be a potent candidate for clinical treatment of the inflammatory bowel disease.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Bingjiao
authors.initials: B
authors.lastname: Yin
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Huifang
authors.initials: H
authors.lastname: Liang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Nin
authors.initials: N
authors.lastname: Niu
authors.forename: Baihua
authors.initials: B
authors.lastname: Li
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jiang
authors.forename: Zhuoya
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D053583:Interleukin-1beta / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000378:metabolism* / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D016209:Interleukin-8; D019151:Peptide Library; D010456:Peptides, Cyclic; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase