Activation of toll-like receptor 3 protects against DSS-induced acute colitis by Matam Vijay-Kumar, Huixia Wu, Jesse D. Aitken, Vasantha L. Kolachala, Andrew S. Neish, Shanthi V. Sitaraman, Andrew T. Gewirtz.
Mimetics of bacterial DNA, given orally or subcutaneously, protect mice from experimental colitis via a toll-like receptor (TLR)-9-dependent mechanism. The goal the study was to define whether synthetic viral RNA, polyinosinic acid:cytidylic acid [poly(I:C)], which is also potent immunomodulator, might affect murine and, if so, such effects were mediated by TLR3, one at least 4 known receptors for this RNA analog.Mice (C57BL6, IL-10KO, TLR3 KO) administered 1.5% dextran sodium sulfate (DSS) in drinking water 7 days. Two hours before treatment with DSS, phosphate-buffered saline (PBS) poly(I:C) 20 mug subcutaneously (s.c.), 100 intragastrically (i.g.).In wildtype s.c. administration dramatically protected against DSS-induced as assessed every parameter analyzed, included body weight, rectal bleeding, colonic myeloperoxidase, histopathology, serum keratinocyte-derived chemokine, amyloid A, and lipocalin-2. In contrast, i.g. offered no protection model nor did its activate innate immune system serologic parameters. Subcutaneous equally well C57BL6 IL-10KO mice, indicating that antiinflammatory cytokine not required protection. Protection ablated KO, protective action analog receptor.Activation on cells are accessible systemic, but oral, results acute inflammation can ensue upon damage gut epithelium. Thus, analog, under clinical trials other inflammatory disorders (e.g., lupus), may have therapeutic value bowel disease.
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