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• Dexmedetomidine has a protective effect on AA rat models. • Invasion, migration, and inflammation of RA-FLSs are inhibited by dexmedetomidine. • DEX can reduce the expression of NLRC5 in RA-FLSs and AA rat models. • NLRC5-RNAi inhibits inflammation, invasion and migration of RA-FLSs. Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by inflammatory synovitis, but its pathogenesis remains unclear. NLRC5 is a newly discovered member of the NLR family that is effective in regulating autoimmunity, inflammatory responses, and cell death processes. Dexmedetomidine (DEX) has been reported to have a variety of pharmacological effects, including anti-inflammatory and analgesic effects. However, the role of DEX in RA has not been explored. In adjuvant-induced arthritis (AA) rat models, DEX (10 μg/kg and 20 μg/kg) reduced the pathological score, the arthritis score, paw swelling volume, and the serum levels of IL-1β, IL-6, IL-17A, and TNF-α. Moreover, by using Western blot and real-time quantitative PCR (RT-qPCR), it was demonstrated that DEX can inhibit the expression of IL-1β, IL-6, MMP-3, MMP-9 and P-P65 in the synovial tissue of AA rats. In human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), DEX (250 nM and 500 nM) was found to inhibit the expression of IL-1β, IL-6, MMP-3, MMP-9, and P-P65 following stimulation with TNF-α. Moreover, DEX can inhibit the invasion and migration of RA-FLSs stimulated by TNF-α. Finally, the expression of NLRC5 in RA-FLSs and AA rat models was also reduced by DEX. After silencing NLRC5 in RA-FLSs, the expression of IL-1β, IL-6, MMP-3, MMP-9, and P-P65, as well as the invasion and migration of cells, were significantly reduced. These results indicate that DEX inhibits the invasion, migration, and inflammation of RA-FLSs by reducing the expression of NLRC5 and inhibiting the NF-κB activation. [ABSTRACT FROM AUTHOR]

• Chronic cold stress activated microglia in the hippocampus of mice. • GABA mediated the activation of microglia. • The NLRP3 inflammasome and NF-κB pathways involved the activation of microglia. Chronic cold stress has long-term dramatic effects on the animal immune and neuroendocrine systems. As one of the important regions of the brain, the hippocampus is the main region involved in response to stressors. Nevertheless, the impact to the hippocampus following cold exposure and the underlying mechanism involved are not clear. To evaluate the response of the hippocampus during chronic cold stress, male C57BL/6 mice were exposed to 4 °C, 3 h per day for 1 week, after which neuroinflammation and the molecular and signaling pathways in the hippocampus response to cold stress were investigated. To confirm the potential mechanism, BV2 cells were treated with γ-aminobutyric acid (GABA) and BAY 11-7082 and MCC950, then the activation of microglia and key proteins involved in the regulation of inflammation were measured. We demonstrated that chronic cold stress induced the activation of microglia, the emergence of neuroinflammation, and the impairment of neurons in the hippocampus, which might be the result of GABA-mediated activation of nod-like receptor protein 3 (NLRP3) inflammasome and the nuclear factor kappa B (NF-κB) signaling pathway. [ABSTRACT FROM AUTHOR]