tailieunhanh - Báo cáo y học: "Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts. | Agarwal et al. Arthritis Research Therapy 2011 13 R3 http content 13 1 R3 RESEARCH ARTICLE Open Access Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts 1 1 2 2 1 Sandeep K Agarwal Minghua Wu Christopher K Livingston Donald H Parks Maureen D Mayes Frank C Arnett1 Filemon K Tan1 Abstract Introduction Increased levels of genes in the type I interferon IFN pathway have been observed in patients with systemic sclerosis SSc or scleroderma. How type I IFN regulates the dermal fibroblast and its participation in the development of dermal fibrosis is not known. We hypothesized that one mechanism by which type I IFN may contribute to dermal fibrosis is through upregulation of specific Toll-like receptors TLRs on dermal fibroblasts. Therefore we investigated the regulation of TLR expression on dermal fibroblasts by IFN. Methods The expression of TLRs was assessed in cultured dermal fibroblasts from control and SSc patients stimulated with IFNa2. The ability of IFNa2 to regulate TLR-induced interleukin IL -6 and CC chemokine ligand 2 production was also assessed. Immunohistochemical analyses were performed to determine whether TLR3 was expressed in skin biopsies in the bleomycin-induced skin fibrosis model and in patients with SSc. Results IFNa2 increased TLR3 expression on human dermal fibroblasts which resulted in enhanced TLR3-induced IL-6 production. SSc fibroblasts have an augmented TLR3 response to IFNa2 relative to control fibroblasts. Pretreatment of fibroblasts with transforming growth factor TGF -p increased TLR3 induction by IFNa2 but coincubation ofTGF-p did not alter TLR3 induction by IFN. Furthermore IFNa2 inhibits but does not completely block the induction of connective tissue growth factor and collagen expression by TGF-pin fibroblasts. TLR3 expression was observed in dermal fibroblasts and inflammatory cells from skin biopsies from patients with SSc as well as in the bleomycin-induced

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