Micheliolide alleviates ankylosing spondylitis (AS) by suppressing the activation of the NLRP3 inflammasome and maintaining the balance of Th1/Th2 via regulating the NF-κB signaling pathway

BACKGROUND: Ankylosing spondylitis (AS) is a common form of inflammatory arthritis. Micheliolide (MCL), a sesquiterpene lactone, is reportedly involved in the alleviation of inflammatory response. This study aimed to investigate the mechanism of MCL in the treatment of AS. METHODS: Mice were randomly divided into five groups: the sham group, the MCL (50 mg/kg) group, the AS model group, the AS + MCL (20 mg/kg) group, and the AS + MCL (50 mg/kg) group. After the addition of the inhibitor celastrol, mice were randomly divided into five groups: the sham group, the AS model group, the AS + MCL (50 mg/kg) group, the AS + Celastrol (1 mg/kg) group, and the AS + Celastrol (1 mg/kg) + MCL (50 mg/kg) group. RESULTS: Compared with the AS model mice, the protein expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18 were decreased after MCL treatment. The protein expression levels of capase-1 p10, IL-1β p17, NOD-like receptor family and pyrin domain containing 3 (NLRP3), caspase-1, and apoptosis-associated speck-like protein (ASC) were also reduced. The protein expression levels of Interferon (IFN)-γ were down-regulated, but levels of IL-4 were increased. Western blotting and immunohistochemistry revealed that the levels of p-IκB α were up-regulated, while the levels of phosphorylated-p65 were down-regulated. After the addition of celastrol, MCL treatment significantly reduced the levels of p-p65, NLRP3, caspase-1, and ASC. Meanwhile, the levels of IFN-γ were markedly down-regulated, but the levels of IL-4 were enhanced. CONCLUSIONS: Our study found that MCL suppressed the activation of NLRP3 inflammasome and maintained the balance of Th1/Th2 via regulating NF-κB signaling. Therefore, MCL could potentially be used to treat AS.