HDAC inhibitor MS-275 attenuates the inflammatory reaction in rat experimental autoimmune prostatitis.

摘要

BACKGROUND: Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of male sex accessory glands and is characterized by a cellular and humoral prostate-specific autoimmune response. EAP shares important clinical and immunological features with human chronic prostatitis and chronic pelvic pain syndrome. MS-275, a potent histone deacetylase inhibitor, has promising anti-inflammatory activities and might be a new agent in the therapy of prostate inflammation. METHODS: EAP rats were treated with MS-275 (5 mg/kg, i.p.) once daily. Using immunohistochemistry and PCR assay, we determined immune cellular responses and infiltration into the prostate glands, and changes of mRNA levels of representative inflammatory molecules in prostate tissue. Changes in Foxp3(+) CD4(+) cell populations of lymph nodes and peripheral blood were analyzed by flow cytometry. Additionally, direct anti-inflammatory effects of MS-275 were investigated in vitro with a macrophage cell line. RESULTS: MS-275 treatment significantly reduced the local accumulation of immune cells and mRNA levels of representative pro-inflammatory molecules in prostate tissue. Furthermore, MS-275 treatment increased percentage of Foxp3(+) CD4(+) Treg cells in lymph nodes and their proportion to CD4(+) cells in peripheral blood, and induced a relative increase of ED2(+) macrophage numbers in EAP prostate. Additional in vitro study showed that MS-275 induced a switch of macrophages from classic M1 to anti-inflammatory M2 phenotype. CONCLUSIONS: In summary, our data demonstrated that MS-275 could effectively suppress inflammatory reaction in EAP, through suppressing immune cells and pro-inflammatory molecules, and inducing anti-inflammatory immune cells and molecules, which may suggest MS-275 as a potential candidate for treatment of inflammatory prostatitis.