Seong-Kyu Kim1, Yoon Jeong Cho2, Jung-Yoon Choe3. 1. Division of Rheumatology, Department of Internal Medicine, Arthritis & Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea. Electronic address: kimsk714@cu.ac.kr. 2. Department of Family Medicine, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea. 3. Division of Rheumatology, Department of Internal Medicine, Arthritis & Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea.
Abstract
OBJECTIVE: There 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). METHODS: A 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. RESULTS: Higher 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. CONCLUSION: This study suggests that the NLRP3 inflammasome may be involved in the pathogenesis of AS and therefore a potential therapeutic target in AS.
OBJECTIVE: There 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). METHODS: A 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. RESULTS: Higher 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. CONCLUSION: This study suggests that the NLRP3 inflammasome may be involved in the pathogenesis of AS and therefore a potential therapeutic target in AS.
Authors: Emily A Caseley; Samuel Lara-Reyna; James A Poulter; Joanne Topping; Clive Carter; Fatima Nadat; Gavin P Spickett; Sinisa Savic; Michael F McDermott Journal: J Clin Immunol Date: 2021-10-21 Impact factor: 8.317