Engagement of Toll-Like Receptor 3 Induces Vascular Endothelial Growth Factor and Interleukin-8 in Human Rheumatoid Synovial Fibroblasts.
10.3904/kjim.2010.25.4.429
- Author:
Su Jin MOON
1
;
Mi Kyung PARK
;
Hye Jwa OH
;
Seon Yeong LEE
;
Seung Ki KWOK
;
Mi La CHO
;
Ji Hyeon JU
;
Kyung Su PARK
;
Ho Youn KIM
;
Sung Hwan PARK
Author Information
1. Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine, Seoul, Korea. rapark@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Toll-like receptor 3;
Arthritis, rheumatoid;
Vascular endothelial growth factor;
Interleukin-8;
Synovial fibroblast
- MeSH:
Arthritis, Rheumatoid/drug therapy/*etiology/metabolism;
Cells, Cultured;
Fibroblasts/metabolism;
Humans;
Interleukin-8/analysis/*biosynthesis/genetics;
NF-kappa B/physiology;
Neovascularization, Pathologic/etiology;
RNA, Messenger/analysis;
Synovial Membrane/cytology/*metabolism;
Toll-Like Receptor 3/analysis/*physiology;
Vascular Endothelial Growth Factor A/analysis/*biosynthesis/genetics
- From:The Korean Journal of Internal Medicine
2010;25(4):429-435
- CountryRepublic of Korea
- Language:English
-
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 fibroblast-like 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-kappaB), 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-kappaB signaling pathway. Therefore, targeting the TLR3 pathway may be a promising approach to preventing pathologic angiogenesis in RA.
