The Inhibiting Effects And Eechanisms Of GTS-21on The Lps-induced Inflammatory Cytokine Production In Raw264.7Cells And The Significanceto The Treatment Of Rheumatoid Arthritis

Objective:The study is indicated to explore whether GTS-21, an α7selective nicotinicacetylcholine receptor agonist, could attenuate LPS-induced inflammatory cytokineproduction and its molecular biological mechanisms, then illuminate the significance to thetreatment of Rheumatoid Arthritis.Methods:1.Murine RAW264.7macrophage cell lines were cultured in DMEM supplementedwith10%FBS in a humidified incubator with5%CO2at37°C.2.The cytotoxicity of GTS-21to RAW264.7cell lines(CCK-8assay).3.The effects of GTS-21to LPS-induced inflammatory cytokines (TNF-α、IL-1、IL-6)production in RAW264.7cell lines (ELISA).4.The effects of GTS-21to LPS-induced activation of NF-κB (NF-κB p-p65、p-IκB、p-IKK) in RAW264.7cell lines (Western-blot).5.The effect of GTS-21to LPS-induced nuclei translocation of NF-κB p65in RAW264.7cell lines (Confocal fluorescence microscopy).Results:In this study, we showed that GTS-21attenuated the LPS-stimulated cytokines(TNF-α、IL-1、IL-6) expression in RAW264.7cells. Moreover, our results showed for thefirst time that GTS-21suppressed LPS-induced activation of NF-κB pathway and thenuclei translocation of NF-κB p65. Conclusion:According to our results, we assumed that GTS-21exhibited its anti-inflammatoryeffects by decreasing the LPS-stimulated cytokines production and the suppression ofactivation of NF-κB pathway and the nuclei translocation of NF-κB p65. As macrophagesare extremely essential to pathogenesis of Rheumatoid Arthritis, our research maycontribute to rational utility and pharmacological study of GTS-21in futureanti-rheumatoid research.