tailieunhanh - Báo cáo y học: "Urokinase-type plasminogen activator and arthritis progression: role in systemic disease with immune complex involvemen"

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: Urokinase-type plasminogen activator and arthritis progression: role in systemic disease with immune complex involvement. | Cook et al. Arthritis Research Therapy 2010 12 R37 http content 12 2 R37 RESEARCH ARTICLE Open Access Urokinase-type plasminogen activator and arthritis progression role in systemic disease with immune complex involvement Andrew D Cook1 2 Christine M De Nardo1 2 Emma L Braine1 2 Amanda L Turner1 2 Ross Vlahos1 2 Kerrie J Way1 2 S Kaye Beckman1 2 Jason C Lenzo1 2 John A Hamilton1 2 Abstract Introduction Urokinase-type plasminogen activator u-PA has been implicated in fibrinolysis cell migration latent cytokine activation cell activation T-cell activation and tissue remodeling all of which are involved in the development of rheumatoid arthritis. Previously u-PA has been reported to play a protective role in monoarticular arthritis models involving mBSA as the antigen but a deleterious role in the systemic polyarticular collagen-induced arthritis CIA model. The aim of the current study is to determine how u-PA might be acting in systemic arthritis models. Methods The CIA model and bone marrow chimeras were used to determine the cellular source of u-PA required for the arthritis development. Gene expression of inflammatory and destructive mediators was measured in joint tissue by quantitiative PCR and protein levels by ELISA. The requirement for u-PA in the type II collagen mAb-induced arthritis CAIA and K BxN serum transfer arthritis models was determined using uPA mice. Neutrophilia was induced in the peritoneal cavity using either ovalbumin anti-ovalbumin or the complement component C5a. Results u-PA from a bone marrow-derived cell was required for the full development of CIA. The disease in uPA mice reconstituted with bone marrrow from C57BL 6 mice was indistinguishable from that in C57BL 6 mice in terms of clincal score histologic features and protein and gene expression of key mediators. uPA mice were resistant to both CAIA and K BxN serum transfer arthritis development. u-PA- - mice developed a reduced neutrophilia and chemokine production