Role of MS19 in alleviating lung inflammation in CTD-ILD by regulating macrophage polarization through inhibiting the expression of IRF5
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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