Article Text

PDF
AB0166 Up-regulation of SOCS3 by calcineurin inhibitor, tacrolimus, suppresses IL-6/SIL-6R-mediated rankl expression in fibroblast-like synoviocytes
  1. W.-T. Chung1,
  2. H. Lee2,
  3. J.H. Kim2,
  4. S.-H. Park2,
  5. J.-Y. Choe2,
  6. S.-K. Kim2
  1. 1Dong-A University College of Medicine, Busan
  2. 2Catholic University of Daegu School of Medicine, Daegu, Korea, Republic Of

Abstract

Objectives Interactions between interleukin-6 (IL-6)/gp130/Janus activated kinase (JAK)/signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling (SOCS) are responsible for the expression of receptor activator of NF-kB ligand (RANKL), essential factor for osteoclastogenesis. We investigated whether calcineurin inhibitor, tacrolimus, suppresses RANKL expression in fibroblast-like synoviocytes through regulation of IL-6-mediated signaling.

Methods RANKL/JAK/STAT/SOCS expressions from IL-6-stimulated fibroblast-like synoviocytes (FLS), cultured from synovium of rheumatoid arthritis (RA) patients, were assessed by western blotting. RANKL levels after tacrolimus were measured by real-time polymerase chain reaction (PCR) and Ensyme-linked immunosorbent assay (ELISA). SOCS3 knockdown FLS using siRNA transfection for SOCS was used to evaluate the effect of tacrolimus on SOCS3. Immunofluorescent staining was also performed to identify the effect of tacrolimus on RANKL and SOCS.

Results We identify that RANKL expression in RA FLS is regulated through IL-6/sIL-6R/JAK2/STAT3/SOCS3 pathway. Tacrolimus inhibits the RANKL expression in IL-6/sIL-6R-stimulated FLS through STAT3 suppression by up-regulation of SOCS3. Tacrolimus more potently suppresses the RANKL expression in FLS, compared to dexamethasone and methotrexate. Among negative regulators of JAK/STAT pathway such as CIS1, SOCS1, and SOCS3, only SOCS3 is regulated by tacrolimus.

Conclusions Tacrolimus might be a potent regulator for osteoclastogenesis through down-regulation of RANKL production of RA FLS.

Disclosure of Interest None Declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.