title: Activation of LXR attenuates collagen-induced arthritis via suppressing BLyS production.
abstract: B-lymphocyte stimulator (BLyS) plays a critical role in the pathogenesis and progression of rheumatoid arthritis (RA). Liver X receptor (LXR), a nuclear receptor, has an important anti-inflammatory effect. However, it is unclear whether the BLyS expression is regulated by LXR. In this study, we found that treatment with LXR agonist in collagen-induced arthritis (CIA) mice significantly attenuated arthritis progression, and markedly decreased BLyS production in serum and splenocytes as well as the production of serum IFNγ and TGFβ. Activation of LXR in B lymphocytes dramatically suppressed the basal and IFNγ/TGFβ-induced BLyS expression. Moreover, LXR agonist prominently suppressed the binding of NF-κB to BLyS promoter region, and decreased the promoter's transcriptional activity. Additionally, activation of LXR obviously repressed IFNγ-induced STAT1 activation and TGFβ-induced SMAD3 activation. These results indicated that downregulation of BLyS may be a novel mechanism by which LXR ameliorates RA, and LXR/BLyS pathway may serve as a novel target for the treatment of RA.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China; Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xilin
authors.initials: X
authors.lastname: Lyu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China. Electronic address: hefengtian2010@hotmail.com.
authors.forename: Fengtian
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China. Electronic address: cqhuanggang@aliyun.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D001565:Benzoates; D001596:Benzylamines; C473027:GW 3965; D000071518:Liver X Receptors; D016328:NF-kappa B; D057093:Orphan Nuclear Receptors; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma
keywords: Arthritis; B lymphocyte; B-lymphocyte stimulator; Gene regulation; Liver X receptor