CXCL16-mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway
dc.contributor.author | Ruth, Jeffrey H. | en_US |
dc.contributor.author | Haas, Christian S. | en_US |
dc.contributor.author | Park, Christy C. | en_US |
dc.contributor.author | Amin, Mohammed Asif | en_US |
dc.contributor.author | Martinez, Rita J. | en_US |
dc.contributor.author | Haines, G. Kenneth III | en_US |
dc.contributor.author | Shahrara, Shiva | en_US |
dc.contributor.author | Campbell, Phillip L. | en_US |
dc.contributor.author | Koch, Alisa E. | en_US |
dc.date.accessioned | 2007-03-19T17:25:19Z | |
dc.date.available | 2007-03-19T17:25:19Z | |
dc.date.issued | 2006-03 | en_US |
dc.identifier.citation | Ruth, Jeffrey H.; Haas, Christian S.; Park, Christy C.; Amin, M. Asif; Martinez, Rita J.; Haines, G. Kenneth; Shahrara, Shiva; Campbell, Phillip L.; Koch, Alisa E. (2006)."CXCL16-mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway." Arthritis & Rheumatism 54(3): 765-778. <http://hdl.handle.net/2027.42/49514> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/49514 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16508941&dopt=citation | en_US |
dc.description.abstract | Objective Rheumatoid arthritis (RA) is characterized by profound mononuclear cell (MNC) recruitment into synovial tissue (ST), thought to be due in part to tumor necrosis factor Α (TNFΑ), a therapeutic target for RA. Although chemokines may also be involved, the mechanisms remain unclear. We undertook this study to examine the participation of CXCL16, a novel chemokine, in recruitment of MNCs to RA ST in vivo and to determine the signal transduction pathways mediating this process. Methods Using a human RA ST–SCID mouse chimera, immunohistochemistry, enzyme-linked immunosorbent assay, real-time reverse transcription–polymerase chain reaction, flow cytometry, and in vitro chemotaxis assays, we defined the expression and function of CXCL16 and its receptor, CXCR6, as well as the signal transduction pathways utilized by them for MNC homing in vitro and in vivo. Results CXCL16 was markedly elevated in RA synovial fluid (SF) samples, being as high as 145 ng/ml. Intense macrophage and lining cell staining for CXCL16 in RA ST correlated with increased CXCL16 messenger RNA levels in RA ST compared with those in osteoarthritis and normal ST. By fluorescence-activated cell sorting analysis, one-half of RA SF monocytes and one-third of memory lymphocytes expressed CXCR6. In vivo recruitment of human MNCs to RA ST implanted in SCID mice occurred in response to intragraft injection of human CXCL16, a response similar to that induced by TNFΑ. Lipofection of MNCs with antisense oligodeoxynucleotides for ERK-1/2 resulted in a 50% decline in recruitment to engrafted RA ST and a 5-fold decline in recruitment to regional lymph nodes. Interestingly, RA ST fibroblasts did not produce CXCL16 in response to TNFΑ in vitro, suggesting that CXCL16 protein may function in large part independently of TNFΑ. Conclusion Taken together, these results point to a unique role for CXCL16 as a premier MNC recruiter in RA and suggest additional therapeutic possibilities, targeting CXCL16, its receptor, or its signaling pathways. | en_US |
dc.format.extent | 741932 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.title | CXCL16-mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Geriatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan Medical School, Ann Arbor, and Northwestern University Feinberg School of Medicine, Chicago, Illinois | en_US |
dc.contributor.affiliationum | University of Michigan Medical School, Ann Arbor, and Northwestern University Feinberg School of Medicine, Chicago, Illinois | en_US |
dc.contributor.affiliationum | University of Michigan Medical School, Ann Arbor, and Northwestern University Feinberg School of Medicine, Chicago, Illinois | en_US |
dc.contributor.affiliationum | University of Michigan Medical School, Ann Arbor, and Northwestern University Feinberg School of Medicine, Chicago, Illinois | en_US |
dc.contributor.affiliationum | University of Michigan Medical School, Ann Arbor, and Northwestern University Feinberg School of Medicine, Chicago, Illinois | en_US |
dc.contributor.affiliationum | University of Michigan Medical School, Ann Arbor, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Veterans Administration Chicago Health Care Medical Center, Chicago, Illinois, and Ann Arbor Veterans Administration, Ann Arbor, Michigan ; University of Michigan Medical School, Department of Medicine, Rheumatology Division, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0680 | en_US |
dc.contributor.affiliationother | Northwestern University Feinberg School of Medicine, Chicago, Illinois | en_US |
dc.contributor.affiliationother | Northwestern University Feinberg School of Medicine, Chicago, Illinois | en_US |
dc.contributor.affiliationother | Northwestern University Feinberg School of Medicine, Chicago, Illinois | en_US |
dc.identifier.pmid | 16508941 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/49514/1/21662_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/art.21662 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe its collections in a way that respects the people and communities who create, use, and are represented in them. We encourage you to Contact Us anonymously if you encounter harmful or problematic language in catalog records or finding aids. More information about our policies and practices is available at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.