Suppressed androgen receptor expression promotes M2 macrophage reprogramming through the STAT3/SOCS3 pathway

Area of Science:

• Cardiovascular Research
• Immunology
• Cell Biology

Background:

• Macrophages are key players in inflammatory cardiovascular diseases, with different phenotypes having opposing roles.
• Previous research indicated that suppressing androgen receptor (AR) alleviates experimental autoimmune myocarditis (EAM).
• The involvement of anti-inflammatory M2 macrophages in this AR-mediated process was previously unclear.

Purpose of the Study:

• To investigate the role of M2 macrophages in AR-suppressed EAM.
• To determine if suppressing AR influences M2 macrophage polarization.
• To explore the molecular mechanisms by which AR affects M2 macrophage function.

Main Methods:

• Utilized experimental autoimmune myocarditis (EAM) models.
• Investigated IL-4 stimulation-induced M2 macrophages.
• Assessed the effects of androgen receptor (AR) suppression using ASC-J9.
• Measured anti-inflammatory cytokines, M2 macrophage-related factors, SOCS3, and STAT3 activation.

Main Results:

• Suppressed AR led to elevated anti-inflammatory cytokines and M2 macrophages in EAM.
• Impaired AR in IL-4 stimulated M2 macrophages increased M2-related factor expression.
• AR suppression promoted M2 polarization by reducing SOCS3 and enhancing STAT3 activation.

Conclusions:

• Androgen receptor (AR) plays a critical role in macrophage polarization.
• Suppressed AR expression promotes the reprogramming of anti-inflammatory M2 macrophages.
• ASC-J9 shows potential as a therapeutic agent for inflammatory cardiomyopathy by modulating macrophage polarization.