TAILIEUCHUNG - Báo cáo y học: "Platelet-derived growth factor and transforming growth factor beta synergistically potentiate inflammatory mediator synthesis by fibroblast-like synoviocytes"

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: Platelet-derived growth factor and transforming growth factor beta synergistically potentiate inflammatory mediator synthesis by fibroblast-like synoviocytes. | Rosengren et al. Arthritis Research Therapy 2010 12 R65 http content 12 2 R65 RESEARCH ARTICLE Open Access Platelet-derived growth factor and transforming growth factor beta synergistically potentiate inflammatory mediator synthesis by fibroblast-like synoviocytes Sanna Rosengren Maripat Corr and David L Boyle Abstract Introduction The objective of this study was to model the effects of transforming growth factor beta TGF-P and platelet-derived growth factor PDGF both present in rheumatoid arthritis RA synovia on the behavior of fibroblastlike synoviocytes FLS in response to pro-inflammatory cytokine interleukin IL 1p tumor necrosis factor-alpha TNFa challenge. Methods Gene and protein expression by fibroblast-like synoviocytes in vitro was studied by quantitative Polymerase Chain Reaction qPCR ELISA and multiplex bead cytokine assays. Intracellular signaling pathway activation was determined by Western blot for phospho-kinases and the use of specific inhibitors. Results In combination TGF-p and PDGF 2GF synergistically augmented TNFa- or ILip-induced matrix metalloproteinase 3 MMP3 IL6 IL8 and macrophage inflammatory protein 1 alpha MIP1a secretion by FLS. Other FLS-derived mediators remained unaffected. Individually neither growth factor significantly potentiated TNFa or ILip-induced MMP3 secretion and only slightly enhanced IL6. The effect of 2GF on TNFa-induced gene expression was transcriptionally mediated blocked by imatinib mesylate and occurred even if 2GF was added as much as four hours prior to TNFa. In addition a 15-minute pulse of 2GF four hours prior to TNFa stimulation yielded a synergistic response. The extracellular-signal-regulated kinase ERK and phosphoinositide 3-kinase PI3K signaling pathways were induced for at least four hours by 2GF as demonstrated by persistently upregulated levels of phospho-Akt and phospho-ERK. However pharmacologic inhibitor studies demonstrated that the potentiating action of 2GF was dependent on .

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