Epigenetic regulation of TIMP-3 expression in human macrophages via physiological and pharmacological modification of histone3 lysine27 (H3K27).
Uncover the epigenetic secrets behind macrophage TIMP-3 expression - a key regulator of immune/inflammatory diseases. Discover how cytokines and pharmacological agents modulate this process, with implications for targeted therapies.
This study investigated the epigenetic regulation of TIMP-3 expression in human macrophages. Using RT-qPCR, the researchers found that the Th2 cytokine IL-4 induces TIMP-3, while the Th1 cytokine IFN-γ suppresses it. Mechanistically, IL-4 increased TIMP-3 through reduced H3K27 trimethylation, while IFN-γ decreased it via reduced H3K27 acetylation. The KDM6B demethylase was identified as a key regulator. Importantly, the KDM6 inhibitor GSK-J4 paradoxically reduced TIMP-3, while the HDAC inhibitor MS-275 reversed IFN-γ's suppressive effects. These findings provide insights into the epigenetic control of macrophage function, with implications for managing immune/inflammatory diseases.