Blocking ERK-1/2 reduces tumor necrosis factor Α–induced interleukin-18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of interleukin-18 binding protein A
dc.contributor.author | Marotte, Hubert | en_US |
dc.contributor.author | Ahmed, Salahuddin | en_US |
dc.contributor.author | Ruth, Jeffrey H. | en_US |
dc.contributor.author | Koch, Alisa E. | en_US |
dc.date.accessioned | 2010-04-14T20:04:07Z | |
dc.date.available | 2011-03-01T16:26:46Z | en_US |
dc.date.issued | 2010-03 | en_US |
dc.identifier.citation | Marotte, Hubert; Ahmed, Salahuddin; Ruth, Jeffrey H.; Koch, Alisa E. (2010). "Blocking ERK-1/2 reduces tumor necrosis factor Α–induced interleukin-18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of interleukin-18 binding protein A." Arthritis & Rheumatism 62(3): 722-731. <http://hdl.handle.net/2027.42/69190> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/69190 | |
dc.description.abstract | Objective To examine the mechanism of regulation of interleukin-18 (IL-18) bioactivity by IL-18 binding protein (IL-18BP) induction. Methods Levels of IL-18 and IL-18BPa in synovial fluid samples from patients with osteoarthritis (OA) or rheumatoid arthritis (RA) were determined by enzyme-linked immunosorbent assays (ELISAs), followed by calculation of free IL-18. IL-18 and IL-18BPa synthesis in RA synovial fibroblasts that had been treated with proinflammatory and antiinflammatory cytokines were assessed by quantitative real-time polymerase chain reaction and ELISA, respectively, followed by IL-18 bioactivity determination using KG-1 cells. Chemical signaling inhibitors were used for determination of the signal transduction pathways involved in IL-18BPa/IL-18 regulation. Tumor necrosis factor Α (TNFΑ)–induced caspase 1 activity was determined by a colorimetric assay. Results IL-18BPa was lower in RA synovial fluid than in OA synovial fluid ( P < 0.05; n = 8), and free IL-18 was higher in RA synovial fluid than in OA synovial fluid. TNFΑ induced RA synovial fibroblast IL-18BPa and IL-18 in a time-dependent manner ( P < 0.05). Evaluation of signaling pathways suggested that TNFΑ induced IL-18 production through the ERK-1/2, protein kinase CΔ (PKCΔ), and Src pathways, whereas IL-18BPa synthesis was mediated through the NFΚB, PKC, Src, and JNK pathways. Furthermore, addition of exogenous IL-18BPa-Fc reduced the RA synovial fibroblast phosphorylation of ERK-1/2 induced by TNFΑ. Conclusion These results suggest that IL-18BPa reduces IL-18 bioactivity induced by TNFΑ, by regulating the ERK-1/2 pathway in RA synovial fibroblasts. Targeting IL-18 bioactivity by induction or addition of IL-18BPa may provide another therapeutic option in the management of RA. | en_US |
dc.format.extent | 248644 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 | Blocking ERK-1/2 reduces tumor necrosis factor Α–induced interleukin-18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of interleukin-18 binding protein A | 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, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor, and VAMC, Ann Arbor, Michigan ; Department of Internal Medicine/Division of Rheumatology, University of Michigan Medical School, BSRB Room 4045, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 | en_US |
dc.identifier.pmid | 20131228 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/69190/1/27269_ftp.pdf | |
dc.identifier.doi | 10.1002/art.27269 | 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 library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information 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.