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Immunol Lett. 2017 Aug;188:1-8. doi: 10.1016/j.imlet.2017.05.011. Epub 2017 May 21.

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

Author information

1
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 137-701, South Korea; Laboratory of Immune Network, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
2
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 137-701, South Korea; IMPACT Biotech, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
3
Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
4
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 137-701, South Korea; Laboratory of Immune Network, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea; IMPACT Biotech, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
5
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 137-701, South Korea; Laboratory of Immune Network, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea; IMPACT Biotech, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address: iammila@catholic.ac.kr.

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.

KEYWORDS:

AMPK; PPARγ; Rheumatoid arthritis (RA); SMILE; Th17 cell; Ursodeoxycholic acid (UDCA)

PMID:
28539269
DOI:
10.1016/j.imlet.2017.05.011
[Indexed for MEDLINE]

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