Article Text

PDF
SAT0007 Resistin Directly Stimulates Chemokine Gene Expressions in Rheumatoid Synovial Fibroblasts: DNA Microarray Analysis
  1. H. Sato,
  2. S. Muraoka,
  3. N. Kusunoki,
  4. M. Kawazoe,
  5. S. Masuoka,
  6. E. Shindo,
  7. N. Fujio,
  8. K. Shikano,
  9. M. Kaburaki,
  10. N. Tanaka,
  11. K. Kaneko,
  12. T. Yamamoto,
  13. T. Hasunuma,
  14. S. Kawai
  1. Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan

Abstract

Background Adipose tissue synthesizes and releases physiologically active molecules that are known as adipokines. Although the most widely discussed biological effects of resistin has been the regulation of glucose homeostasis and insulin sensitivity, resistin is now considered to represent a new family of compounds that act as mediators of immune and inflammatory processes [1]. We previously reported that serum resistin concentration was elevated in patients with rheumatoid arthritis (RA) and it was associated with serum C-reactive protein concentration [2]. However, the direct effects of resistin on rheumatoid synovial fibroblasts (RSFs) have not been clarified yet.

Objectives The aim of this study is to determine the direct effects of resistin on RSFs by DNA microarray analysis.

Methods Synovial tissues were obtained at total knee replacement operation from patients with RA who gave consent to use their tissue for research. This study was approved by the Ethics Committee of Toho University School of Medicine. RSFs were harvested from the synovial tissues of RA patients. After 18h incubation with different concentrations of resistin (0, 100 and 1000 ng/mL), total RNA was extracted from the cells and the gene expression profile of RSFs was analyzed by DNA microarray (Agilent Technologies, CA, USA). In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to confirm the result of microarray analysis.

Results The DNA microarray analysis revealed that 45 inflammation-related genes were up-regulated in RSFs in concentration dependent manners when we applied equal to or more than a 3 fold increase to cut-off value for gene expression. We picked up 13 chemokine (CCL2, CCL3, CCL4, CCL7, CCL20, CCL3L3, CXCL1, CXCL2, CXCL3, CXCL6, CXCL8, CXCL10, and CXCR4) genes out of these 45 candidates. Concentration-dependent up-regulation of only CXCL8, CXCL1, CXCL6, CCL2 and CCL7 gene expressions were confirmed by RT-PCR.

Conclusions In this study, we demonstrated that resistin increased gene expressions of 45 inflammation-related molecules in RSFs, when screened by DNA microarray analysis. Resistin-induced chemokines were identified as CXCL8, CXCL1, CXCL6, CCL2 and CCL7. Since they are known as essential mediators in synovial inflammation of RA, resistin may possibly play an important role in pathogenesis of RA.

References

  1. Gόmez R, Conde J, Scotece M, Gόmez-Reino JJ, Lago F, Gualillo O. What's new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol. 2011 Aug 2;7(9):528-36.

  2. Yoshino T, Kusunoki N, Tanaka N, Kaneko K, Kusunoki Y, Endo H, Hasunuma T, Kawai S. Elevated serum levels of resistin, leptin, and adiponectin are associated with C-reactive protein and also other clinical conditions in rheumatoid arthritis. Intern Med. 2011;50(4):269-75.

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.