Modulation of the colonic epithelial cell responses and amelioration of inflammation by CD80 blockade in TNBS colitis.
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.
Srinivasan
Mythily
M
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
Summerlin
Don-Jon
DJ
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
D018122:B7-1 Antigen; C530950:CD80-CAP; D009842:Oligopeptides; D051193:Toll-Like Receptors; D012313:RNA; D014302:Trinitrobenzenesulfonic Acid