The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Engagement of Toll-Like Receptor 3 Induces Vascular Endothelial Growth Factor and Interleukin-8 in Human Rheumatoid Synovial Fibroblasts

  • Moon, Su-Jin (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine) ;
  • Park, Mi-Kyung (Rheumatism Research Center, Catholic Institute of Medical Science) ;
  • Oh, Hye-Jwa (Rheumatism Research Center, Catholic Institute of Medical Science) ;
  • Lee, Seon-Yeong (Rheumatism Research Center, Catholic Institute of Medical Science) ;
  • Kwok, Seung-Ki (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine) ;
  • Cho, Mi-La (Rheumatism Research Center, Catholic Institute of Medical Science) ;
  • Ju, Ji-Hyeon (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine) ;
  • Park, Kyung-Su (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine) ;
  • Kim, Ho-Youn (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine) ;
  • Park, Sung-Hwan (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine)
  • Received : 2010.01.27
  • Accepted : 2010.08.04
  • Published : 2010.12.01
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Abstract

Background/Aims: Angiogenesis, which is a critical step in the initiation and progression of rheumatoid arthritis (RA), involves pro-angiogenic factors, including interleukin (IL)-8 and vascular endothelial growth factor (VEGF). We investigated the role of Toll-like receptor 3 (TLR3) in the regulation of pro-angiogenic factors in RA fibroblastlike synoviocytes (FLS). Methods: FLS were isolated from RA synovial tissues and stimulated with the TLR3 ligand, poly (I:C). The levels of VEGF and IL-8 in the culture supernatants were measured using enzyme-linked immunosorbent assays, and the mRNA levels were assessed by semiquantitative reverse transcription-polymerase chain reaction. The expression patterns of VEGF and IL-8 in the RA synovium and osteoarthritis (OA) synovium were compared using immunohistochemistry. Results: The expression levels of TLR3, VEGF, and IL-8 were significantly higher in the RA synovium than in the OA synovium. VEGF and IL-8 production were increased in the culture supernatants of RA FLS stimulated with poly (I:C), and the genes for these proteins were up-regulated at the transcriptional level after poly (I:C) treatment. Treatment with inhibitors of nuclear factor-kappaB (NF-${\kappa}B$), i.e., pyrrolidine dithiocarbamate and parthenolide, abrogated the stimulatory effect of poly (I:C) on the production of VEGF and IL-8 in RA FLS. Conclusions: Our results suggest that the activation of TLR3 in RA FLS promotes the production of proangiogenic factors, in a process that is mediated by the NF-${\kappa}B$ signaling pathway. Therefore, targeting the TLR3 pathway may be a promising approach to preventing pathologic angiogenesis in RA.

Keywords

References

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