Objective To determine the therapeutic effect of MS 19 on pulmonary inflammation in mice with connective tissue disease related interstitial lung disease(CTD-ILD)by targeting IRF5 and related mechanism.Methods Animal experiments:CTD-ILD mouse models were constructed and treated with MS 19 to determine the effect of MS 19 on pulmonary inflammation in CTD-ILD mice.Cell experiments:RAW264.7 cells were transfected with OE-IRF5,and then treated with MS19 to study the effect of MS19 on IRF5-mediated M1 polarization and inflammatory responses of the macrophages.Results Animal experiments:CTD-ILD mice showed significant pulmonary inflammation,with elevated expression of IRF5,M1 polarization of macrophages,and expression of pro-inflammatory cytokines(TNF-α,IL-6,and IL-1β)in bronchoalveolar lavage fluid(BALF).While the CTD-ILD mice treated with MS 19,their pulmonary inflammation was alleviated,and expression of IRF5,M1 polarization of macrophages and expression of pro-inflammatory cytokines were all decreased in BALF.Cell experiments:LPS induced an increase in M1 polarization and expression of pro-inflammatory cytokines in the macrophages.After transfection of OE-IRF5,Ml polarization of macrophages and expression of pro-inflammatory cytokines increased.After the MS 19 treatment,Ml polarization of macrophages and expression of pro-inflammatory cytokines decreased.Conclusion MS 19 improves pulmonary inflammation in CTD-ILD by targeting and inhibiting IRF5,thereby providing potential targets and candidate drugs for the prevention and treatment of CTD-ILD.
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