Airborne particulate matter enhances with monosodium urate crystals the secretion of IL-1β by human immune cells

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Abstract Gout is driven by an interleukin-1 β -mediated intense innate immune reaction to monosodium urate (MSU) crystals (MSUc). In cell culture models of inflammatory gout there is a synergistic effect of phagocytosis of MSUc and TLR2 and TLR4 activation by agonists such as free fatty acid and lipopolysaccharide (LPS) in NLRP3-inflammasome activation and IL-1 β secretion. A substantial number of gout patients do not report a dietary trigger, and observational studies associate airborne particulate matter with incident gout and flares. Airborne particulate matter contains LPS and airborne-derived particulate matter stimulates IL-1 β secretion in cell culture. We hypothesized that air-borne particulate matter could co-stimulate, with MSUc, IL-1 β secretion and inflammation. We tested the hypothesis using MSUc with extracted airborne PM 4 in human cells (the THP-1 monocyte cell line, primary human monocytes and PBMCs) or carbon black particles with ozone (CB+O 3 ) in a murine foot-pad injection model of gout. There was strong NLRP3-inflammasome-dependent co-stimulation of IL-1 β secretion in THP-1 cells with PM 4 +MSUc and a moderate additive effect in primary human PBMCs. However, there was no added effect on IL-1 β secretion of PM 4 in isolated primary human monocytes. Inhalation of CB+O 3 persistently exacerbated MSUc-induced murine paw inflammation, with an increase of alveolar/lavage macrophages that contained CB+O 3 particles and increased lavage expression of IL-1 β . In conclusion, airborne-derived PM 4 particulate matter enhanced MSUc-induced IL-1 β secretion in THP-1 cells and PBMCs. Combined with exacerbation of MSUc-induced inflammation by fine particulate matter in in vivo experiments, these data provide evidence that exposure to fine particulate matter may play a role in the etiology of gout.

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