Interleukin-18 as an in vivo mediator of monocyte recruitment in rodent models of rheumatoid arthritis
dc.contributor.author | Ruth, Jeffrey H | |
dc.contributor.author | Park, Christy C | |
dc.contributor.author | Amin, M A | |
dc.contributor.author | Lesch, Charles | |
dc.contributor.author | Marotte, Hubert | |
dc.contributor.author | Shahrara, Shiva | |
dc.contributor.author | Koch, Alisa E | |
dc.date.accessioned | 2015-08-07T17:25:31Z | |
dc.date.available | 2015-08-07T17:25:31Z | |
dc.date.issued | 2010-06-16 | |
dc.identifier.citation | Arthritis Research & Therapy. 2010 Jun 16;12(3):R118 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/112330 | en_US |
dc.description.abstract | 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), and IL-17. Signal-transduction experiments revealed that IL-18 signals through p38 and ERK½ 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 that IL-18 may serve a hierarchic position for initiating joint inflammatory responses. | |
dc.title | Interleukin-18 as an in vivo mediator of monocyte recruitment in rodent models of rheumatoid arthritis | |
dc.type | Article | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/112330/1/13075_2010_Article_2890.pdf | |
dc.identifier.doi | 10.1186/ar3055 | en_US |
dc.language.rfc3066 | en | |
dc.rights.holder | Ruth et al. | |
dc.date.updated | 2015-08-07T17:25:31Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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