PMID- 29274624 OWN - NLM STAT- MEDLINE DCOM- 20180831 LR - 20180831 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 55 DP - 2018 Feb TI - Interferon regulatory factor 5 (IRF5) regulates the expression of matrix metalloproteinase-3 (MMP-3) in human chondrocytes. PG - 231-236 LID - S1567-5769(17)30457-5 [pii] LID - 10.1016/j.intimp.2017.11.035 [doi] AB - Matrix metalloproteinase-3 (MMP-3) plays a pivotal role in the destruction of articular cartilage in osteoarthritis (OA). The regulation of gene expression of MMP-3 is complicated. Interferon regulatory factor 5 (IRF5) is a member of the interferon regulatory factor family of transcription factors. Little information regarding the biological function of IRF5 on chondrocytes and the pathogenesis of OA has been reported. In the current study, for the first time, we report that IRF5 is expressed in human primary chondrocytes and human chondrosarcoma cell line SW1353 cells. In addition, IRF5 is upregulated in response to TNF-alpha treatment in a dose dependent manner. Interestingly, IRF5 is significantly higher in chondrocytes from OA patients compared to those from normal subjects. Notably, IRF5 mediates TNF-alpha- induced expression of MMP-3 in chondrocytes. Overexpression of IRF5 promotes the expression of MMP-3, however, knockdown of IRF5 reduces the expression of MMP-3. Mechanistically, IRF5 is able to enhance the transcription of MMP-3 by binding to its promoter. Also, we found that NF-kappaB was involved in the effects of IRF-5 on MMP-3 expression. These findings suggest that IRF5 might be a novel pharmacological target for the treatment of OA and RA. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Guo, Lin AU - Guo L AD - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Hao, Ruihu AU - Hao R AD - Department of Orthopedics, Affiliated Zhongshan hospital of Dalian University, Xi'an, China. FAU - Tian, Fengde AU - Tian F AD - Department of Orthopedics, Affiliated Zhongshan hospital of Dalian University, Xi'an, China. FAU - An, Ning AU - An N AD - Department of Orthopedics, Affiliated Zhongshan hospital of Dalian University, Xi'an, China. FAU - Wang, Kunzheng AU - Wang K AD - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: wangkz068@126.com. LA - eng PT - Journal Article DEP - 20171222 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (IRF5 protein, human) RN - 0 (Interferon Regulatory Factors) RN - 0 (NF-kappa B) RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Cartilage, Articular/*pathology MH - Chondrosarcoma/*genetics/immunology MH - Gene Expression Regulation MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Interferon Regulatory Factors/*genetics/metabolism MH - Matrix Metalloproteinase 3/genetics/*metabolism MH - Molecular Targeted Therapy MH - NF-kappa B/metabolism MH - Osteoarthritis/*genetics/immunology MH - RNA, Small Interfering/genetics MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Chondrocytes OT - Interferon regulatory factor 5 (IRF5) OT - Matrix metalloproteinase-3 OT - Osteoarthritis EDAT- 2017/12/24 06:00 MHDA- 2018/09/01 06:00 CRDT- 2017/12/24 06:00 PHST- 2017/09/05 00:00 [received] PHST- 2017/11/23 00:00 [revised] PHST- 2017/11/27 00:00 [accepted] PHST- 2017/12/24 06:00 [pubmed] PHST- 2018/09/01 06:00 [medline] PHST- 2017/12/24 06:00 [entrez] AID - S1567-5769(17)30457-5 [pii] AID - 10.1016/j.intimp.2017.11.035 [doi] PST - ppublish SO - Int Immunopharmacol. 2018 Feb;55:231-236. doi: 10.1016/j.intimp.2017.11.035. Epub 2017 Dec 22.