1-7-bis(4-hydroxy-3-methoxyphenyl)-1-4-6-heptatrien-3-one and Autoimmune-Diseases

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.. 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.. 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.. AR inhibition alleviates the inflammatory response and tissue apoptosis by enhancing autophagy, especially in macrophages.

Topics: Adenine; Androgen Receptor Antagonists; Animals; Anti-Inflammatory Agents; Apoptosis; Autoimmune Diseases; Autophagy; Curcumin; Disease Models, Animal; Macrophages; Male; Mice, Inbred BALB C; Myocarditis; Myocardium

Cardiac fibrosis is an important cardiac remodeling event in the development of inflammation dilated cardiomyopathy （iDCM）. We have previously observed that degradation enhancer of androgen receptor (ASC-J9

Topics: Animals; Autoimmune Diseases; Cardiotonic Agents; Collagen; Curcumin; Fibroblasts; Fibrosis; Gene Expression Regulation; Humans; Mice; Mice, Inbred BALB C; MicroRNAs; Myocarditis; Myocardium; Myosin Heavy Chains; Primary Cell Culture; Receptors, Androgen; Signal Transduction

Macrophages are important mediators in inflammatory cardiovascular diseases. Experimental autoimmune myocarditis (EAM) is characterized by pronounced macrophages infiltration, cardiac necrosis and cardiac fibrosis. Androgen receptor (AR) is a regulator of immune system which can control macrophages' infiltration and function in various inflammatory-related diseases. However, the effect of AR on the inflammatory response in EAM is unknown. Our study aims to investigate the potential role of AR on the development of autoimmune myocarditis.. AR facilitated EAM development, and targeting AR with ASC-J9 attenuated cardiac injury and dysfunction by inhibiting macrophages polarization towards M1 macrophages.

Topics: Androgen Receptor Antagonists; Animals; Autoimmune Diseases; Blotting, Western; Cell Line; Curcumin; Heart Injuries; Lipopolysaccharides; Macrophages; Mice, Inbred BALB C; Monocytes; Myocarditis; Myocardium; Receptors, Androgen; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; STAT5 Transcription Factor; Suppressor of Cytokine Signaling 1 Protein; Tumor Necrosis Factor-alpha

Prostatitis is a common disease contributing to 8% of all urologist visits. Yet the etiology and effective treatment remain to be further elucidated. Using a non-obese diabetes mouse model that can be induced by autoimmune response for the spontaneous development of prostatitis, we found that injection of the ASC-J9® at 75 mg/Kg body weight/48 hours led to significantly suppressed prostatitis that was accompanied with reduction of lymphocyte infiltration with reduced CD4+ T cells in prostate. In vitro studies with a co-culture system also confirmed that ASC-J9® treatment could suppress the CD4+ T cell migration to prostate stromal cells. Mechanisms dissection indicated that ASC-J9® can suppress CD4+ T cell migration via decreasing the cytokine CCL2 in vitro and in vivo, and restoring CCL2 could interrupt the ASC-J9® suppressed CD4+ T cell migration. Together, results from in vivo and in vitro studies suggest that ASC-J9® can suppress prostatitis by altering the autoimmune response induced by CD4+ T cell recruitment, and using ASC-J9® may help us to develop a potential new therapy to battle the prostatitis with little side effects.

Topics: Animals; Autoimmune Diseases; CD4-Positive T-Lymphocytes; Cell Line; Cell Movement; Chemokine CCL2; Curcumin; Humans; Male; Mice, Inbred NOD; Prostate; Prostatitis; Signal Transduction; Stromal Cells