tailieunhanh - Báo cáo y học: " The effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts"

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: The effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts. | Mattyasovszky et al Arthritis Research Therapy 2010 12 R4 http content 12 1 R4 RESEARCH ARTICLE Open Access The effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts Stefan G Mattyasovszky 21 Alexander Hofmann21 Christoph Brochhausen2 Ulrike Ritz1 Sebastian Kuhn1 Jochen Wollstadter1 Hendrik Schulze-Koops3 Lars P Muller1 Bernhard Watzer4 and Pol M Rommens1 Abstract Introduction Previous studies have shown that the number of myoblastically differentiated fibroblasts known as myofibroblasts MFs is significantly increased in stiff joint capsules indicating their crucial role in the pathogenesis of post-traumatic joint stiffness. Although the mode of MFs function has been well defined for different diseases associated with tissue fibrosis the underlying mechanisms of their regulation in the pathogenesis of post-traumatic joint capsule contracture are largely unknown. Methods In this study we examined the impact of the pro-inflammatory cytokine tumor necrosis factor-alpha TNF-a on cellular functions of human joint capsule MFs. MFs were challenged with different concentrations of TNF-a with or without both its specifically inactivating antibody infliximab IFX and cyclooxygenase-2 COX2 inhibitor diclofenac. Cell proliferation gene expression of both alpha-smooth muscle actin a-SMA and collagen type I the synthesis of prostaglandin derivates E2 F1A and F2A as well as the ability to contract the extracellular matrix were assayed in monolayers and in a three-dimensional collagen gel contraction model. The a-SMA and COX2 protein expressions were evaluated by immunofluorescence staining and Western blot analysis. Results The results indicate that TNF-a promotes cell viability and proliferation of MFs but significantly inhibits the contraction of the extracellular matrix in a dose-dependent manner. This effect was associated with downregulation of a-SMA and collagen type I by TNF-a application. .