NLRP3 inflammasomes and NLRP3 inflammasome-derived proinflammatory cytokines in peripheral blood mononuclear cells of patients with ankylosing spondylitis

Abstract

ObjectiveThere is some evidence that an enhanced Th17 response is attributable to interleukin-1β (IL-1β) matured by activation of the NLRP3 inflammasome. In this study, we assessed the expression of NLRP3 inflammasome components and their associated proinflammatory cytokines in patients with ankylosing spondylitis (AS). MethodsA total of 23 male patients with AS and 29 male controls were recruited and peripheral blood mononuclear cells (PBMCs) were collected. Transcript and protein expression of NLRP3, caspase-1, ASC, IL-1β, IL-17A, and IL-23 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay, respectively. Data were analyzed using Spearman's correlation coefficient, Mann-Whitney U test, and receiver operating characteristic curves. ResultsHigher mRNA expression of NLRP3, ASC, IL-1β, IL-17A, and IL-23 was noted in the PBMCs of AS patients than those of controls (p = 0.013, p = 0.001, p = 0.002, p = 0.011, and p = 0.037, respectively). Similarly, protein expression of NLRP3, caspase-1, ASC, IL-1β, IL-17A, and IL-23 was higher in the AS group than the control group. There were significant correlations among NLRP3, caspase-1, ASC, IL-1β, IL-17A, and IL-23 expression in patients with AS, except for a weak association between NLRP3 and IL-17A. Treatment of cultured PBMCs with 10 ng of lipopolysaccharide induced NLRP3, caspase-1, ASC, IL-1β, IL-17A, and IL-23 expression, which was marked suppressed by treatment with ascorbic acid. ConclusionThis study suggests that the NLRP3 inflammasome may be involved in the pathogenesis of AS and therefore a potential therapeutic target in AS.