Androgen receptor inhibition alleviated inflammation in experimental autoimmune myocarditis by increasing autophagy in macrophages.

OBJECTIVE: Experimental autoimmune myocarditis (EAM) is characterized by pronounced macrophage infiltration, cardiac necrosis, and cardiac fibrosis. Our previous studies have demonstrated that suppressed androgen receptor (AR) enables anti-inflammation to promote tissue repair by decreasing M1 macrophages and increasing M2 macrophages in an EAM model. Given that autophagy mediates inflammatory response in macrophages, we investigated whether AR inhibition executes its protective role in inflammation through the autophagy pathway in EAM. MATERIALS AND METHODS: To determine whether AR inhibition can perform its anti-inflammatory effects by upregulating autophagy, we pre-treated mice with 3-methyl adenine (3-MA), a pharmacological inhibitor of autophagy. Immunofluorescence assay and Western blot were used to detect autophagy levels and autophagy activity in five different groups. Immunofluorescence marked F4/80 and LC3 to illustrate the autophagy level in macrophages. TUNEL assays were used to detect the apoptosis level in heart tissue of five different groups. RESULTS: We demonstrated that AR inhibition resolves injury with sustained inhibition of inflammatory cytokines associated with enhanced autophagy, especially in macrophages. Increased LC3II/I expression corroborated complete autolysosome formation detected by electron microscopy and correlated with degradation of SQSTM1/p62 in the AR inhibition group by Western blot. These effects could be reversed within 3-MA, a pharmacological inhibitor of autophagy. Specifically, pharmacological inhibition of autophagy increased apoptosis and inflammation, which could be attenuated by AR inhibition. CONCLUSIONS: AR inhibition alleviates the inflammatory response and tissue apoptosis by enhancing autophagy, especially in macrophages.

Involvement of descending inhibition in the effect of acupuncture on the splanchnically evoked potential in the orbital cortex of cat.

The possible involvement of descending inhibition in the effect of acupuncture on the transmission of visceral afferent impulses has been investigated. Averaged splanchnically evoked potentials were recorded in the orbital cortex of the unanesthetized immobilized cat. The evoked orbital potentials could be inhibited by electroacupuncture. Section of the descending inhibitory pathway which is known to be located in the dorsolateral funiculi of the spinal cord produced marked diminution of the acupuncture inhibitory effect on the evoked cortical potentials with needles either inserted in the hindlimb or in the forelimb. Since the afferent impulses from the forelimb entered the cord above the level of section (T3-4), the ascending pathway for acupuncture signals to the supraspinal structure was thus left intact. Destruction of the pontobulbar reticular formation including mainly the nucleus raphe magnus produced the same diminution of the acupuncture effect. The results indicate that the ascending visceral afferent impulses are blocked at the level of the spinal cord by the acupuncture-induced descending impulses from the supraspinal center, probably the nucleus raphe magnus.