Role of the NLRP3 inflammasome in the transient release of IL-1β induced by monosodium urate crystals in human fibroblast-like synoviocytes

Background: To investigate whether monosodium urate (MSU) crystals induce interleukin (IL)-1 beta in human fibroblast-like synoviocytes (FLS), and whether the NLRP3 inflammasome is involved in the inflammatory mechanism. Methods: Human FLS isolated from explants of synovial tissue were stimulated with MSU crystals (0.001 to 0.5 mg/ml) for different time course (6 hours to 48 hours). The expressions of IL-1 beta, IL-6, TNF-alpha and NLRP3 were evaluated with ELISA, Western blot and quantitative real-time PCR. Results: Exposure of FLS to MSU crystals transiently induced a significant increase in IL-1 beta expression in culture medium with a peak at 6 h. The mRNA level of IL-1 beta in the FLS cells had a similar pattern at this time point. Changes in IL-6 and TNF-alpha expression were not observed. Simultaneously, intercellular pro-IL-1 beta was detected at 6 h. Furthermore, MSU crystals also induced NLRP3 mRNA and protein expression at 6 h to 48 h after MSU treatment. Conclusions: MSU crystals directly increased IL-1 beta and intercellular NLRP3 expression in FLS cells. It is suggested that the NLRP3 inflammasome may be associated with IL-1 beta in FLS treated with MSU. Altogether, MSU could induce production and release of IL-1 beta through the NLRP3 inflammasome in human synoviocytes.