Abstract
Background and Objectives: Gouty arthritis is an acute inflammatory response caused by the precipitation of monosodium urate (MSU) crystals in joints. The triggering of MSU leads to increased production of inflammatory cytokines, such as interleukin-1β, which in turn lead to the formation of macromolecular complexes, referred to as inflammasomes. Thorough characterization of the NLRP3 inflammasome can be used as an indicator of an immune response against harmful stimuli. Cardamonin is a chalcone, mainly found in the seeds of Alpinia katsumadai, and exhibits anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines in vitro. However, the mechanism by which cardamonin treatment alleviates gouty arthritis has yet to be fully elucidated. Materials and Methods: In vitro or in vivo models were used to study whether cardamonimn inhibited NLRP3 inflammasome activation or suppressed gouty inflammation. Results: In the current study, we determined that most NLRP3 was released passively after MSU stimulation, and this release of NLRP3 promoted caspase-1 activation and IL-1β secretion. Cardamonin was shown to decrease both the activity of caspase-1 and secretion of IL-1β in J774A.1 macrophage cells subjected to MSU stimulation. Cardamonin was also shown to attenuate the production of COX-2 in MSU-stimulated J774A.1 macrophage cells. Finally, cardamonin reduced the thickness of the synovial lining and the infiltration of gouty arthritis in a rat model. Conclusions: Overall, cardamonin significantly attenuated IL-1β secretion, caspase-1 activity, and COX-2 production stimulated by MSU. These findings provide new insights into the molecular mechanisms underlying the effects of cardamonin treatment for gouty arthritis.
Highlights
Cyclooxygenase-2 (COX-2) is a pivotal enzyme involved in maintaining inflammation through the catalysis of prostaglandin E2 and has been linked to the development of autoimmune disorders, coronary artery disease, and cancer [1,2]
Evidence obtained in this study suggests that monosodium urate (MSU) crystal-induced inflammation involves phagocytosis activated by the NLRP3 inflammasome, leading to the secretion of IL-1β from resident macrophages
Our findings reveal that cardamonin exerts anti-inflammatory effects by inhibiting activation of the NLRP3 inflammasome in J774A.1 macrophages in vitro
Summary
Cyclooxygenase-2 (COX-2) is a pivotal enzyme involved in maintaining inflammation through the catalysis of prostaglandin E2 and has been linked to the development of autoimmune disorders, coronary artery disease, and cancer [1,2]. COX-2 appears to be the dominant source of prostaglandins in inflammation and no doubt contributes to the development of acute inflammation in gouty arthritis attacks. Gouty arthritis is an acute inflammatory response resulting from the precipitation of monosodium urate (MSU) crystals in joints. In an animal model of acute gout, the injection of MSU crystals was shown to trigger the production of proinflammatory cytokines, such as interleukin-1β (IL-1β) [7,8]. The release of IL-1β as a key regulatory proinflammatory cytokine in gout cases has been shown to promote the influx of neutrophils into the synovium and joint fluid, which is a pathological hallmark of an acute inflammatory attack [9]. Gouty arthritis is an acute inflammatory response caused by the precipitation of monosodium urate (MSU) crystals in joints. The mechanism by which cardamonin treatment alleviates gouty arthritis has yet to be fully elucidated
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