title: Modulation of the colonic epithelial cell responses and amelioration of inflammation by CD80 blockade in TNBS colitis.
abstract: Inflammatory bowel diseases (IBD) result from dysregulated immune responses to the luminal antigens initiated by the colonic epithelial cells (CEC) and propagated by activated CD4+ T cells. Biological therapies are being developed that suppress inflammation and promote epithelial homeostasis. Treatment with the CD80-competitive antagonist peptide (CD80-CAP) has been shown to suppress T cell responses in multiple disease models. Here we investigated the effect of the CD80-CAP on the CEC responses in experimental colitis. Balb/c mice induced with trinitrobenzene sulfonic acid (TNBS) colitis were administered CD80-CAP/control peptide/vehicle. Administration of the CD80-CAP decreased microscopic inflammation and restored the expression of TLR-2, 3, 4 and 5 mRNA in the CEC of colitis mice to physiological levels. Furthermore, the CD80-CAP treatment suppressed Th1 cytokines and enhanced Th2 responses by the CEC in colitis mice. In conclusion, CD80-CAP administration ameliorated TNBS colitis by reducing the inflammatory cell infiltration and modulating the CEC response potentially restoring mucosal tolerance.
authors.affiliation: Department of Oral Pathology, Medicine and Radiology, School of Dentistry, Indiana University Purdue University at Indianapolis, 1121, West Michigan Street, Indianapolis, IN 46202, USA. mysriniv@iupui.edu
authors.forename: Mythily
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Don-Jon
authors.initials: DJ
authors.lastname: Summerlin
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003092:Colitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D005434:Flow Cytometry; D006651:Histocytochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D018122:B7-1 Antigen; C530950:CD80-CAP; D009842:Oligopeptides; D051193:Toll-Like Receptors; D012313:RNA; D014302:Trinitrobenzenesulfonic Acid