Involvement of nuclear factor k B in the regulation of cyclooxygenase-2 expression by interleukin-1 in rheumatoid synoviocytes
dc.contributor.author | Crofford, Leslie J. | en_US |
dc.contributor.author | Tan, Bing | en_US |
dc.contributor.author | McCarthy, Conor J. | en_US |
dc.contributor.author | Hla, Timothy | en_US |
dc.date.accessioned | 2006-04-28T16:25:42Z | |
dc.date.available | 2006-04-28T16:25:42Z | |
dc.date.issued | 1997-02 | en_US |
dc.identifier.citation | Crofford, Leslie J.; Tan, Bing; McCarthy, Conor J.; Hla, Timothy (1997)."Involvement of nuclear factor k B in the regulation of cyclooxygenase-2 expression by interleukin-1 in rheumatoid synoviocytes." Arthritis & Rheumatism 40(2): 226-236. <http://hdl.handle.net/2027.42/37810> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/37810 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=9041934&dopt=citation | en_US |
dc.description.abstract | Objective . To evaluate involvement of the transcription factor nuclear factor k B (NF- k B) in the increased expression of cyclooxygenase-2 (COX-2) stimulated by interleukin-1Β (IL-1Β) in primary rheumatoid synoviocytes. Methods . We treated early-passage rheumatoid synoviocytes with IL-1Β and examined the time course of NF- k B translocation to the nucleus by Western blot analysis, as well as NF- k B binding to the COX-2 promoter/enhancer by electrophoretic mobility shift assay. We correlated the time course of NF- k B binding with expression of COX-2 messenger RNA (mRNA) and protein. Synoviocytes were then treated with either sense or antisense phosphorothioate-modified oligonucleotides derived from the transcription start site of the human NF- k B p65 RNA. We analyzed NF- k B binding to the COX-2 promoter and COX-2 protein levels after these treatments. Results . IL-1Β rapidly stimulated the translocation of the p65, p50, and c-rel NF- k B subunits from the cytoplasm to the nucleus. Electrophoretic mobility shift assay demonstrated binding to 2 NF- k B sites within the COX-2 promoter/enhancer, with a time course identical to that of nuclear localization of NF- k B. Supershift analysis revealed that binding activity was due primarily to the p65–p50 heterodimer and the p50 homodimer. With appropriate lag time after NF- k B binding, COX-2 mRNA and protein were increased. Pretreatment of RA synoviocytes with NF- k B p65 antisense oligonucleotides resulted in decreased binding to the COX-2 promoter and decreased COX-2 protein expression. Conclusion . These data demonstrate that signaling via the NF- k B pathway is involved in regulation of COX-2 expression induced by IL-1Β in RA synoviocytes. | en_US |
dc.format.extent | 1090631 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | John Wiley & Sons, Inc. | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Rheumatology | en_US |
dc.title | Involvement of nuclear factor k B in the regulation of cyclooxygenase-2 expression by interleukin-1 in rheumatoid synoviocytes | 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 ; Department of Internal Medicine, Rheumatology Division, University of Michigan Medical Center, R4032 Kresge II, 200 Zina Pitcher Place, Ann Arbor, MI 48109-0574 | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationother | Holland- Laboratory, American Red Cross, Rockville, Maryland | en_US |
dc.identifier.pmid | 9041934 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/37810/1/1780400207_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/art.1780400207 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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