原创力文档interleukin-18 as an in vivo mediator of monocyte recruitment in rodent models of rheumatoid arthritisinterleukin-18单核细胞的体内中介招聘在类风湿性关节炎的动物模型.pdfVIP
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interleukin-18 as an in vivo mediator of monocyte recruitment in rodent models of rheumatoid arthritisinterleukin-18单核细胞的体内中介招聘在类风湿性关节炎的动物模型
Ruth et al. Arthritis Research Therapy 2010, 12:R118
/content/12/3/R118
R E S E A R C H A R T I C L E Open Access
Research article
Interleukin-18 as an in vivo mediator of monocyte
recruitment in rodent models of rheumatoid
arthritis
1 2 1 1 1 2 1,3
Jeffrey H Ruth* , Christy C Park , M Asif Amin , Charles Lesch , Hubert Marotte , Shiva Shahrara and Alisa E Koch
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 gene-
knockout mouse joint homogenates during ZIA, including macrophage inflammatory protein-3α (MIP-3α/CCL20),
vascular endothelial cell growth factor (VEGF)
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