tailieunhanh - Báo cáo y học: "Interleukin-18 as an in vivo mediator of monocyte recruitment in rodent models of rheumatoid arthritis"

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: Interleukin-18 as an in vivo mediator of monocyte recruitment in rodent models of rheumatoid arthritis. | Ruth et al. Arthritis Research Therapy 2010 12 R118 http content 12 3 R118 RESEARCH ARTICLE Open Access Interleukin-18 as an in vivo mediator of monocyte recruitment in rodent models of rheumatoid arthritis Jeffrey H Ruth 1 Christy C Park2 M Asif Amin1 Charles Lesch1 Hubert Marotte1 Shiva Shahrara2 and Alisa E Koch1 3 Abstract Introduction The function of interleukin-18 IL-18 was investigated in pertinent animal models of rodent rheumatoid arthritis RA to determine its proinflammatory and monocyte recruitment properties. Methods We used a modified Boyden chemotaxis system to examine monocyte recruitment to recombinant human rhu IL-18 in vitro. Monocyte recruitment to rhuIL-18 was then tested in vivo by using an RA synovial tissue ST severe combined immunodeficient SCID mouse chimera. We defined monocyte-specific signal-transduction pathways induced by rhuIL-18 with Western blotting analysis and linked this to in vitro monocyte chemotactic activity. Finally the ability of IL-18 to induce a cytokine cascade during acute joint inflammatory responses was examined by inducing wild-type Wt and IL-18 gene-knockout mice with zymosan-induced arthritis ZIA . Results We found that intragraft injected rhuIL-18 was a robust monocyte recruitment factor to both human ST and regional inguinal murine lymph node LN tissue. IL-18 gene-knockout mice also showed pronounced reductions in joint inflammation during ZIA compared with Wt mice. Many proinflammatory cytokines were reduced in IL-18 geneknockout mouse joint homogenates during ZIA including macrophage inflammatory protein-3a MIP-3a CCL20 vascular endothelial cell growth factor VEGF and IL-17. Signal-transduction experiments revealed that IL-18 signals through p38 and ERK in monocytes and that IL-18-mediated in vitro monocyte chemotaxis can be significantly inhibited by disruption of this pathway. Conclusions Our data suggest that IL-18 may be produced in acute inflammatory responses and support the notion