Engagement of Toll-Like Receptor 3 Induces Vascular Endothelial Growth Factor and Interleukin-8 in Human Rheumatoid Synovial Fibroblasts
The Korean Journal of Internal Medicine
;
: 429-435, 2010.
Article
in English
| WPRIM
| ID: wpr-192808
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 (IC). 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 (IC), and the genes for these proteins were up-regulated at the transcriptional level after poly (IC) treatment. Treatment with inhibitors of nuclear factor-kappaB (NF-kappaB), i.e., pyrrolidine dithiocarbamate and parthenolide, abrogated the stimulatory effect of poly (IC) 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Arthritis, Rheumatoid
/
Synovial Membrane
/
RNA, Messenger
/
Cells, Cultured
/
Interleukin-8
/
NF-kappa B
/
Vascular Endothelial Growth Factor A
/
Toll-Like Receptor 3
/
Fibroblasts
/
Neovascularization, Pathologic
Limits:
Humans
Language:
English
Journal:
The Korean Journal of Internal Medicine
Year:
2010
Type:
Article
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