The Effects of Interleukin-17 on Production of Matrix Metalloproteinase-3 in Cultured Rheumatoid Arthritis Synoviocytes / 대한류마티스학회지

OBJECTIVE: To investigate the effect of interleukin-17 (IL-17) on the production of matrix metalloproteinase-3 (MMP-3) and the expression of MMP-3 mRNA in rheumatoid arthritis synoviocytes. METHODS: Fibroblast-like synovial cells (FLS) were prepared from the synovial tissues of rheumatoid arthritis patients and cultured in the presence of various concentration of IL-17. The production of MMP-3 and expression of MMP-3 mRNA were determined by sandwitch ELISA and real-time quantitative RT-PCR. RESULTS: In ELISA, stimulation of FLS by IL-17 with 5, 10, 20, 40 ng/mL concentrations increased the production of MMP-3 by 2.7, 2.9, 3.1, 3.6 fold after 24 hours and 9.9, 10, 11, 12 fold after 48 hours over the constitutive levels of unstimulated FLS. In real-time quantitative RT-PCR, stimulation of FLS by IL-17 with 5, 10, 20, 40 ng/mL concentrations increased the MMP-3/beta-actin mRNA ratio by 3.2, 5.7, 9.9, 30.5 fold after 24 hours over the constitutive levels of unstimulated FLS. CONCLUSIONS: IL-17 may be involved in the joint destruction in rheumatoid arthritis by enhancing the production of MMP-3 from rheumatoid arthritis synoviocytes.

The Effects of Interleukin-17 on Production of Vascular Endothelial Growth Factor in Cultured Rheumatoid Arthritis Synoviocytes / 대한류마티스학회지

OBJECTIVE: To investigate the the effects of interleukin-17 (IL-17)on the production of vascular endothelial growth factor (VEGF)from cultured rheumatoid arthritis synoviocytes. METHODS: Fibroblast-like synovial cells(FLS)were prepared from the synovial tissues of rheumatoid arthritis patients and cultured in the presence of IL-17, IL-17 with or without transforming growth factor-beta(TGF-beta),tumor necrosis factor-alpha(TNF-alpha)and interleukin-1 beta(IL-1 beta).VEGF levels were determined in the culture supernatants by sandwitch ELISA. RESULTS: Stimulation of FLS by serial concentration of IL-17,TGF-beta,TNF-alpha,IL-1 beta increased the production of VEGF by 2.1-2.7,2.2-3.0,2.0-2.9,2.3-3.1 fold over the constitutive levels of unstimulated FLS.Stimulation of FLS by IL- 17 with TGF-beta or TNF-alpha or IL-1 beta also increased the production of VEGF accord-ing to culture periods by 1.6-1.8,1.1-1.9,1.5-1.7 fold over the levels stimulated with TGF-beta or TNF-alpha or IL-1 beta,respectively.This results indicated that IL-17 increased the effect of TGF-beta,TNF-alpha,IL-1 beta on FLS,leading synergistic enhancement of VEGF production. CONCLUSION: IL-17 may be involved in the neovascularization in rheumatoid synovitis by enhancing the production of VEGF.