Background: To investigate whether monosodium urate (MSU) crystals induce interleukin (IL)-1β 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-1β, IL-6, TNF-α 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-1β expression in culture medium with a peak at 6 h. The mRNA level of IL-1β in the FLS cells had a similar pattern at this time point. Changes in IL-6 and TNF-α expression were not observed. Simultaneously, intercellular pro-IL-1β 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-1β and intercellular NLRP3 expression in FLS cells. It is suggested that the NLRP3 inflammasome may be associated with IL-1β in FLS treated with MSU. Altogether, MSU could induce production and release of IL-1β through the NLRP3 inflammasome in human synoviocytes.
Keywords: IL-1β; Inflammasome; MSU; NLRP3; Synoviocytes.