Blocking of interferon regulatory factor 1 reduces tumor necrosis factor α–induced interleukin‐18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of interleukin‐18 binding protein a: Role of the nuclear interferon regulatory factor 1–NF‐κB–c‐jun complex
dc.contributor.author | Marotte, Hubert | en_US |
dc.contributor.author | Tsou, Pei‐suen | en_US |
dc.contributor.author | Rabquer, Bradley J. | en_US |
dc.contributor.author | Pinney, Adam J. | en_US |
dc.contributor.author | Fedorova, Tatiana | en_US |
dc.contributor.author | Lalwani, Nalin | en_US |
dc.contributor.author | Koch, Alisa E. | en_US |
dc.date.accessioned | 2011-12-05T18:34:39Z | |
dc.date.available | 2013-01-02T16:33:06Z | en_US |
dc.date.issued | 2011-11 | en_US |
dc.identifier.citation | Marotte, Hubert; Tsou, Pei‐suen ; Rabquer, Bradley J.; Pinney, Adam J.; Fedorova, Tatiana; Lalwani, Nalin; Koch, Alisa E. (2011). "Blocking of interferon regulatory factor 1 reduces tumor necrosis factor αâ induced interleukinâ 18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of interleukinâ 18 binding protein a: Role of the nuclear interferon regulatory factor 1â NFâ κBâ câ jun complex." Arthritis & Rheumatism 63(11): 3253-3262. <http://hdl.handle.net/2027.42/88092> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/88092 | |
dc.description.abstract | Objective To examine the role of interferon regulatory factor 1 (IRF‐1) in tumor necrosis factor α (TNFα)–induced interleukin‐18 binding protein a (IL‐18BPa) expression in rheumatoid arthritis synovial fibroblasts (RASFs). Methods TNFα‐induced IRF‐1 expression was assessed by real‐time quantitative polymerase chain reaction and Western blotting. The effect of TNFα on IRF‐1 was assessed using nuclear and cytoplasmic extracts, Western blots, and immunofluorescence. Chemical inhibitors of NF‐κB or MAP kinases were used to analyze the signaling pathways of TNFα‐induced IRF‐1 expression and IRF‐1 nuclear translocation. Control and IRF‐1 small interfering RNA (siRNA) were used to analyze the effect of IRF‐1 down‐regulation on TNFα‐induced IL‐18BP expression. IL‐18BPa expression was assessed by enzyme‐linked immunosorbent assay, and IL‐18 was assessed at the transcription and bioactivity levels using KG‐1 cells. Results TNFα induced RASF IRF‐1 expression at the messenger RNA and protein levels, with a maximal effect at 2 hours ( P < 0.05; n ≥ 3). Furthermore, TNFα induced nuclear translocation of IRF‐1, with maximal translocation at 2 hours (∼6 fold‐induction) ( P < 0.05; n = 4). Blocking of the NF‐κB or JNK‐2 pathways reduced TNFα‐induced IRF‐1 nuclear translocation by 35% and 50%, respectively ( P < 0.05; n ≥ 4). Using siRNA to knock down IRF‐1, we observed reduced IL‐18BPa expression. Additionally, IL‐18 bioactivity was higher when siRNA was used to knock down IRF‐1 expression. Conclusion These results show that IRF‐1 is a key regulator of IL‐18BPa expression and IL‐18 bioactivity in RASFs. Regulation of IRF‐1 will be a new therapeutic target in RA. | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.title | Blocking of interferon regulatory factor 1 reduces tumor necrosis factor α–induced interleukin‐18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of interleukin‐18 binding protein a: Role of the nuclear interferon regulatory factor 1–NF‐κB–c‐jun complex | 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 | en_US |
dc.contributor.affiliationum | VA Medical Center, Ann Arbor, Michigan and University of Michigan Medical School, Ann Arbor | en_US |
dc.contributor.affiliationum | 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 | 21834067 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/88092/1/30583_ftp.pdf | |
dc.identifier.doi | 10.1002/art.30583 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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