OBJECTIVE: To determine the ability of interleukin-4 (IL-4) to inhibit the degradation of proteoglycan in bovine articular cartilage explants stimulated by human interleukin-1 (IL-1 alpha), tumor necrosis factor (TNF-alpha), a combination of TNF-alpha and IL-1 alpha, and lipopolysaccharide (LPS). METHODS: 35SO4 radiolabelled bovine radiocarpal cartilage explants were treated with IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS, plus various concentrations of IL-4 for 72 h. Proteoglycan released to the media was analyzed by scintillation counting and composite gel electrophoresis. Media samples were also analyzed by Western immunoblotting for metalloproteinases and TIMP. RESULTS: IL-4 significantly reduced the cartilage proteoglycan degradation induced by IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS (50% inhibitory concentration, IC50 for IL-4 ranged from about 15 to 50 ng/ml). Western blotting showed that media stromelysin levels were increased by IL-1 alpha, TNF-alpha, and LPS, but that IL-4 had no observable effect. Composite gel electrophoresis demonstrated quantitative and qualitative differences in proteoglycan degradation after IL-4 treatment. CONCLUSION: IL-4 has a potent inhibitory effect on cartilage degradation after stimulation with IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS. These results suggest that IL-4 should be investigated further for therapeutic value as a chondroprotective agent for the treatment of arthritis.
OBJECTIVE: To determine the ability of interleukin-4 (IL-4) to inhibit the degradation of proteoglycan in bovinearticular cartilage explants stimulated by humaninterleukin-1 (IL-1 alpha), tumor necrosis factor (TNF-alpha), a combination of TNF-alpha and IL-1 alpha, and lipopolysaccharide (LPS). METHODS:35SO4 radiolabelled bovine radiocarpal cartilage explants were treated with IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS, plus various concentrations of IL-4 for 72 h. Proteoglycan released to the media was analyzed by scintillation counting and composite gel electrophoresis. Media samples were also analyzed by Western immunoblotting for metalloproteinases and TIMP. RESULTS:IL-4 significantly reduced the cartilage proteoglycan degradation induced by IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS (50% inhibitory concentration, IC50 for IL-4 ranged from about 15 to 50 ng/ml). Western blotting showed that media stromelysin levels were increased by IL-1 alpha, TNF-alpha, and LPS, but that IL-4 had no observable effect. Composite gel electrophoresis demonstrated quantitative and qualitative differences in proteoglycan degradation after IL-4 treatment. CONCLUSION:IL-4 has a potent inhibitory effect on cartilage degradation after stimulation with IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS. These results suggest that IL-4 should be investigated further for therapeutic value as a chondroprotective agent for the treatment of arthritis.
Authors: E M van Helvoort; H M de Visser; F P J G Lafeber; K Coeleveld; S Versteeg; H H Weinans; J Popov-Celeketic; N Eijkelkamp; S C Mastbergen Journal: Cartilage Date: 2021-06-23 Impact factor: 4.634