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AB0146 Ursolic Acid Ameliorates Autoimmune Arthritis via Suppression of TH17 and B Cell Differentiation
  1. S.-K. Kwok1,
  2. J. Lee1,
  3. J.H. Koh1,
  4. H.K. Min1,
  5. J.Y. Kang1,
  6. Y.S. Suh1,
  7. J.-H. Lee1,
  8. S.-M. Jung1,
  9. J.Y. Lee1,
  10. J.-M. Kim2,
  11. J.H. Ju1,
  12. K.-S. Park1,
  13. H.-Y. Kim3,
  14. S.-H. Park1
  1. 1Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's hospital, The Catholic University of Korea, Seoul
  2. 2Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center, Daegu
  3. 3Division of Rheumatology, Department of Internal Medicine, Konkuk University Hospital, School of Medicine, Seoul, Korea, Republic Of


Background Ursolic acid (UA) is a pentacytclic triterpenoid compound which is ubiquitously present in plants.

Objectives Based on its known anti-inflammatory and anti-oxidative effect, this study was undertaken to investigate the effect of UA on collagen-induced arthritis (CIA) and to delineate the underlying mechanism.

Methods UA (150mg/kg) or 10% dimethyl sulfoxide was injected intraperitoneally three times a week to mice with CIA from the day 14 after immunization. The expressions of proinflammatory cytokines and molecules associated with oxidative stress in arthritic joints were measured by immunohistochemical staining. The number of CD4+IL-17+ cells or CD4+CD25+Foxp3+ cells or phosphorylated (p) STAT3 + cells was determined by confocal immunostaining of the spleen or flow cytometry analysis of splenocytes. The level of mRNA expression and immunoglobulin was analyzed by real time RT-PCR and ELISA, respectively.

Results UA injection prevented clinical arthritis incidence and joint inflammation in mice with CIA. A significant reduction in pSTAT3 and resultant decrease in the number of Th17 was observed with UA treatment. Consistently, the expression of IL-17 and retinoic acid orphan receptor (ROR)γt was markedly reduced with UA. Although the expression of Foxp3 was unaffected, the number of Treg cells was increased with UA treatment. There was a marked reduction in type II collagen-specific immunoglobulin G production. When IL-21-or LPS-stimulated CD19+ B cells were cultured in the presence or absence of UA, the mRNA expression of markers associated with B cell activation (Bcl-6), plasma cell differentiation (Blimp-1) and isotype switching (activation-induced deaminase) was markedly reduced with UA treatment.

Conclusions Our findings suggest that UA can regulate Th17 and reciprocally promote Treg cells by inhibiting expression of ROR γt and pSTAT3. UA also inhibits plasma cell differentiation, resulting in a reduction of immunoglobulin production. By targeting pathogenic Th17 and immunoglobulin production, UA may be a novel therapeutic for treatment of autoimmune arthritis and other Th17-related diseases.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.3181

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