Abstract
BackgroundTo 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.MethodsHuman 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.ResultsExposure 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.ConclusionsMSU 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-015-0070-7) contains supplementary material, which is available to authorized users.
Highlights
To investigate whether monosodium urate (MSU) crystals induce interleukin (IL)-1β in human fibroblast-like synoviocytes (FLS), and whether the nucleotide-binding domainlike receptor protein 3 (NLRP3) inflammasome is involved in the inflammatory mechanism
The results indicated that 50 ug/ml of MSU induced a significant increase in IL-1β after 6 hours, but not at other time points (Figure 1A)
There were no significant differences in levels of IL-6 (Figure 1B) and TNFα (Figure 1C) in FLS exposed to different concentrations of MSU at all exposure periods
Summary
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. Gout is one of inflammatory arthritis due to deposition of monosodium urate (MSU) crystals in synovial fluid and joints [1]. When MSU crystals were injected into the peritoneum in an animal model of acute gout, it induced the production of proinflammatory cytokines such as interleukin-1β (IL-1β) [2]. Pro-inflammatory cytokines play a critical role in the inflammatory reaction induced by MSU-crystals [6,7]. It is suggested by several studies that IL-1β, the pathological hallmark of the acute inflammatory attack, is a key regulatory pro-inflammatory cytokine in gout, which promotes a neutrophil influx into the synovium and joint fluid [8,9]. IL-1β plays a crucial role in driving the transition from the acute phase of arthritis to the chronic irreversible phase [10]
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