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: Yan Huang, Xiaohong Fu, Xilin Lyu, Zhizhen Xu, Zhicheng He, Yan Zhang, Yijun Zeng, Fengtian He, Gang Huang
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 161 Issue 2 Pg. 339-47 (Dec 2015) ISSN: 1521-7035 [Electronic] United States
• PMID: 26431776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• B-Cell Activating Factor
• Benzoates
• Benzylamines
• GW 3965
• Liver X Receptors
• NF-kappa B
• Orphan Nuclear Receptors
• STAT1 Transcription Factor
• STAT3 Transcription Factor
• Transforming Growth Factor beta
• Interferon-gamma

Topics

• Animals
• Arthritis, Experimental (genetics, metabolism, prevention & control)
• B-Cell Activating Factor (genetics, metabolism)
• B-Lymphocytes (drug effects, metabolism)
• Benzoates (pharmacology)
• Benzylamines (pharmacology)
• Blotting, Western
• Cells, Cultured
• Gene Expression (drug effects)
• Interferon-gamma (blood, metabolism)
• Liver X Receptors
• Male
• Mice, Inbred DBA
• NF-kappa B (metabolism)
• Orphan Nuclear Receptors (agonists, metabolism)
• Promoter Regions, Genetic (genetics)
• Protein Binding (drug effects)
• Reverse Transcriptase Polymerase Chain Reaction
• STAT1 Transcription Factor (metabolism)
• STAT3 Transcription Factor (metabolism)
• Transforming Growth Factor beta (blood, metabolism)