Cellular signalling · 2026
IRF5 promotes the polarization of M1 macrophages and aggravates pulmonary inflammation in connective tissue disease-related interstitial lung disease (CTD-ILD) by regulating IFN-β.
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Chen Shanshan, Ming Qianwen, Yi Lishan, Wang Xiaohong
Аннотация
BACKGROUND: Interferon regulatory factor 5 (IRF5) plays a vital role in proinflammatory M1 macrophages and is involved in their polarization. We aimed to explore the mechanism of action by which IRF5 participates in pulmonary inflammation in connective tissue disease-related interstitial lung disease (CTD-ILD).
METHODS: mRNA and protein levels were determined by qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assays were conducted to confirm the targeted relationship between IRF5 and interferon (IFN)-β. ELISA was performed to measure the levels of proinflammatory factors (interleukin (IL)-6, TNF-α, and IL-1β). IRF5 and CD86 expression levels were analyzed by flow cytometry. The nuclear location of IRF5 was detected by immunofluorescence. A double luciferase reporter assay was performed to confirm that IRF5 targets the IFN-β promoter. Hematoxylin and eosin (HE) staining was conducted to assess the histopathology of pulmonary.
RESULTS: IRF5 and IFN-β levels in peripheral blood were increased in CTD-ILD patients. IRF5 enhanced IFN-β expression by directly binding to its promoter. IRF5 promoted the M1-type polarization of macrophages by activating IFN-β. MS19 suppressed IFN-β expression by inhibiting the activation of IRF5. MS19 repressed M1-type polarization of RAW264.7 cell induced by LPS- through regulating IRF5. MS19 improved pulmonary inflammation in CTD-ILD model mice by inhibiting the M1-type polarization of macrophages via the IRF5/IFN-β axis.
CONCLUSION: IRF5 activated IFN-β transcription by targeting the IFN-β promoter, ultimately promoting the M1-type polarization of macrophages and aggravating inflammation in CTD-ILD, and the effects were alleviated by treated with MS19.
METHODS: mRNA and protein levels were determined by qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assays were conducted to confirm the targeted relationship between IRF5 and interferon (IFN)-β. ELISA was performed to measure the levels of proinflammatory factors (interleukin (IL)-6, TNF-α, and IL-1β). IRF5 and CD86 expression levels were analyzed by flow cytometry. The nuclear location of IRF5 was detected by immunofluorescence. A double luciferase reporter assay was performed to confirm that IRF5 targets the IFN-β promoter. Hematoxylin and eosin (HE) staining was conducted to assess the histopathology of pulmonary.
RESULTS: IRF5 and IFN-β levels in peripheral blood were increased in CTD-ILD patients. IRF5 enhanced IFN-β expression by directly binding to its promoter. IRF5 promoted the M1-type polarization of macrophages by activating IFN-β. MS19 suppressed IFN-β expression by inhibiting the activation of IRF5. MS19 repressed M1-type polarization of RAW264.7 cell induced by LPS- through regulating IRF5. MS19 improved pulmonary inflammation in CTD-ILD model mice by inhibiting the M1-type polarization of macrophages via the IRF5/IFN-β axis.
CONCLUSION: IRF5 activated IFN-β transcription by targeting the IFN-β promoter, ultimately promoting the M1-type polarization of macrophages and aggravating inflammation in CTD-ILD, and the effects were alleviated by treated with MS19.