Activation Status of NLRP3 Inflammasome in Peripheral Blood Mononuclear Cells From Patients With Gout Flare

Abstract

Background/Objective Although gout flares are featured by systemic signs of inflammation, cellular sources of inflammatory mediators are not yet properly characterized. Our objective was to evaluate serum levels and gene expression in peripheral blood mononuclear cells (PBMCs) of several molecules associated with the activation of NLRP3 inflammasome. Methods Fifteen patients with gout flare and 15 individuals with asymptomatic hyperuricemia were cross-sectionally studied. Serum levels of interleukin 1β (IL-1β), IL-18, monocyte chemoattractant protein 1/chemokine (C-C motif) ligand 2 (CCL2), and vascular cell adhesion molecule 1 were measured as a reflection of systemic inflammation, whereas the expression of NLRP3, CASP1, IL18, and CCL2 genes was measured to assess the inflammatory characteristics of PBMCs. Results Serum levels of IL-1β (1.27 [0.07–1.99] pg/mL vs. 0 [0–0.82] pg/mL, p = 0.032) and vascular cell adhesion molecule 1 (606 [435–748] pg/mL vs. 349 [305–422] pg/mL, p = 0.014) were significantly higher in patients with gout flare than in individuals with asymptomatic hyperuricemia, whereas differences in IL-18 and monocyte chemoattractant protein 1/CCL2 were not found. Notably, no differences were observed in the expression of NLRP3, CASP1, IL18, or CCL2 in PBMCs from individuals of one or another group. Conclusions Systemic inflammation during gout flares does not appear to be associated with NLRP3 inflammasome activation in PBMCs, suggesting that it may represent the systemic spread of local (synovial) inflammation to monosodium urate crystals, which provides a rationale for redirecting anti-inflammatory therapy from a systemic approach to one centered on the inflamed joint.

Degenerative joint disease induced by repeated intra-articular injections of monosodium urate crystals in rats as investigated by translational imaging

“…This was expected, as IL-1β is produced as a direct consequence of inflammasome activation with MSU crystals following LPS priming 6 . The characteristic influx of neutrophils and macrophages during a gout flare is coordinated by cytokines/chemokines including IL-1β, IL-8 (CXCL8), MCP-1 (CCL2) and MIP1 (CCL3) 27 , 28 . Upregulation of these mediators was observed in our model following intra-articular challenge with MSU/LPS.…”

Degenerative Joint Disease Induced by Repeated Intra-Articular Injections of Monosodium Urate Crystals in Rats as Investigated by Translational Imaging

“…This was expected, as IL-1b is produced as a direct consequence of in ammasome activation with MSU crystals following LPS priming 6 . The characteristic in ux of neutrophils and macrophages during a gout are is coordinated by cytokines/chemokines including IL-1b, IL-8 (CXCL8), MCP-1 (CCL2) and MIP1 (CCL3) 18,19 . Upregulation of these mediators was observed in our model following single or repeated intra-articular challenge with MSU/LPS.…”

Active components from Lagotis brachystachya maintain uric acid homeostasis by inhibiting renal TLR4-NLRP3 signaling in hyperuricemic mice

“…The MeOH-H 2 O (3:7) eluate was subsequently chromatographed on a silica gel column (9×60 cm, 200-300 mesh) and eluted with CH 2 Cl 2 -CH 3 OH (100: 2, 100: 4, 100: 6, 100:8), and then eluted by ODS column chromatography gradient and repeated recrystallization to obtain the active compounds. 1 H and 13 C NMR spectroscopic analysis were performed to con rm the structures of active compounds as luteolin, luteoloside and apigenin, respectively (Fig. 1).…”