Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways
dc.contributor.author | Amin, Mohammed Asif | en_US |
dc.contributor.author | Mansfield, Pamela J. | en_US |
dc.contributor.author | Pakozdi, Angela | en_US |
dc.contributor.author | Campbell, Phillip L. | en_US |
dc.contributor.author | Ahmed, Salahuddin | en_US |
dc.contributor.author | Martinez, Rita J. | en_US |
dc.contributor.author | Koch, Alisa E. | en_US |
dc.date.accessioned | 2007-09-20T18:37:44Z | |
dc.date.available | 2008-09-08T14:25:14Z | en_US |
dc.date.issued | 2007-06 | en_US |
dc.identifier.citation | Amin, Mohammad A.; Mansfield, Pamela J.; Pakozdi, Angela; Campbell, Phillip L.; Ahmed, Salahuddin; Martinez, Rita J.; Koch, Alisa E. (2007)."Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways." Arthritis & Rheumatism 56(6): 1787-1797. <http://hdl.handle.net/2027.42/56041> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/56041 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17530707&dopt=citation | en_US |
dc.description.abstract | Objective Interleukin-18 (IL-18) is a proinflammatory cytokine implicated in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to examine the role of IL-18 in up-regulating secretion of the angiogenic factors stromal cell–derived factor 1Α (SDF-1Α)/CXCL12, monocyte chemoattractant protein 1 (MCP-1)/CCL2, and vascular endothelial growth factor (VEGF) in RA synovial tissue (ST) fibroblasts, and the underlying signaling mechanisms involved. Methods We used enzyme-linked immunosorbent assays, Western blotting, and chemical inhibitors/antisense oligodeoxynucleotides to signaling intermediates to assess the role of IL-18. Results IL-18 significantly enhanced the production of SDF-1Α/CXCL12, MCP-1/CCL2, and VEGF in RA ST fibroblasts, in a time- and concentration-dependent manner. IL-18–induced SDF-1Α/CXCL12 up-regulation was dependent on JNK, p38 MAPK, phosphatidylinositol 3-kinase (PI3K), and NFΚB. While IL-18–induced production of SDF-1Α/CXCL12 was also dependent on protein kinase CΔ (PKCΔ), production of MCP-1/CCL2 was dependent on PKCΑ, not PKCΔ. Additionally, RA ST fibroblast IL-18–induced MCP-1/CCL2 production was mediated by JNK, PI3K, and NFΚB. In contrast, IL-18 did not induce secretion of RA ST fibroblast MCP-1/CCL2 or VEGF via p38 MAPK. IL-18–induced RA ST fibroblast production of VEGF was mediated mainly by JNK-2, PKCΑ, and NFΚB. IL-18 induced phosphorylation of JNK, PKCΔ, p38 MAPK, and activating transcription factor 2 (ATF-2) in RA ST fibroblasts in a time-dependent manner, with JNK-2 being upstream of PKCΔ, ATF-2, and NFΚB. Conclusion These data support the notion that IL-18 has a unique role in inducing the secretion of angiogenic SDF-1Α/CXCL12, MCP-1/CCL2, and VEGF in RA ST fibroblasts, via distinct signaling intermediates. | en_US |
dc.format.extent | 340126 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 | Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways | 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 Health System, Ann Arbor ; Department of Internal Medicine/Division of Rheumatology, University of Michigan Medical School, 4428 BSRB, 109 Zina Pitcher Drive, Ann Arbor, MI 48109-2200 | en_US |
dc.contributor.affiliationum | University of Michigan Health System, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan Health System, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan Health System, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan Health System, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan Health System, Ann Arbor | en_US |
dc.contributor.affiliationum | Department of Veterans Affairs and University of Michigan Health System, Ann Arbor | en_US |
dc.identifier.pmid | 17530707 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/56041/1/22705_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/art.22705 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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