Ursodeoxycholic acid attenuates experimental autoimmune arthritis by targeting Th17 and inducing pAMPK and transcriptional corepressor SMILE.

Abstract

BACKGROUND Ursodeoxycholic acid (UDCA) has been known that UDCA has prominent effects on liver, however, there is little known about its influence on autoimmune disease. Here, the benefit of UDCA on arthritis rheumatoid (RA) in vivo was tested. METHODS RA mouse were induced using collagen II (CIA, collagen induced arthritis) where the disease severity or UDCA-related signaling pathway such as AMP-activated protein kinase (AMPK) or small heterodimer partner interacting leucine zipper protein (SMILE) was evaluated by westerblot and immunohistochemical staining. Gene expression was measured by realtime-polymerase chain reaction (PCR). RESULTS The administration of UDCA effectively alleviated the arthritic score and incidence with decreased cartilage damage and lipid metabolic parameters. UDCA also suppressed the secretion of pro-inflammatory cytokines. It was confirmed that UDCA upregulated the expression of SMILE and transcriptional activity of PPARγ via controlling AMPK or p38 activity. CONCLUSIONS In the present study, the therapeutic effect of UDCA inducing SMILE through AMPK activation in rheumatoid arthritis mouse as well as other autoimmune disease was proposed.

DOI: 10.1016/j.imlet.2017.05.011

Cite this paper

@article{Lee2017UrsodeoxycholicAA, title={Ursodeoxycholic acid attenuates experimental autoimmune arthritis by targeting Th17 and inducing pAMPK and transcriptional corepressor SMILE.}, author={Eun Jeong Lee and Jeong-Eun Kwon and Min-Jung Park and Kyung-Ah Jung and Da-Som Kim and Eun-Kyung Kim and Seung hoon Lee and Jong Young Choi and Sung Hwan Park and Mi-la Cho}, journal={Immunology letters}, year={2017}, volume={188}, pages={1-8} }