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Updated: Jun 2, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
HDAC inhibitor MS-275 attenuates the inflammatory reaction in rat experimental autoimmune prostatitis
Zhi-Yuan Zhang1, Hermann J Schluesener
1Institute of Pathology and Neuropathology, University of Tuebingen, Tuebingen, Germany. zhiyuan.zhang@medizin.uni-tuebingen.de
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.
Insights
MS-275, a histone deacetylase inhibitor, effectively reduced inflammation in experimental autoimmune prostatitis (EAP) by suppressing immune cells and pro-inflammatory molecules. It also promoted anti-inflammatory immune cells, suggesting its potential for treating prostatitis.
Area of Science:
- Immunology
- Pharmacology
- Urology
Background:
- Experimental autoimmune prostatitis (EAP) is an inflammatory disease of male accessory glands with autoimmune characteristics.
- EAP shares similarities with human chronic prostatitis and chronic pelvic pain syndrome.
- MS-275, a histone deacetylase inhibitor, exhibits anti-inflammatory properties, indicating potential therapeutic value for prostate inflammation.
Purpose of the Study:
- To investigate the therapeutic potential of MS-275 in treating experimental autoimmune prostatitis (EAP).
- To evaluate the effects of MS-275 on immune cell responses and inflammatory markers in EAP.
Main Methods:
- EAP rats were treated daily with MS-275 (5 mg/kg, i.p.).
- Immune cell infiltration, mRNA levels of inflammatory molecules, and regulatory T cell (Treg) populations were analyzed using immunohistochemistry, PCR, and flow cytometry.
- In vitro studies assessed the direct anti-inflammatory effects of MS-275 on macrophages.
Main Results:
- MS-275 treatment significantly reduced immune cell infiltration and pro-inflammatory molecule mRNA levels in prostate tissue.
- MS-275 increased the percentage of Foxp3(+) CD4(+) Treg cells in lymph nodes and peripheral blood.
- MS-275 promoted a shift in macrophages towards an anti-inflammatory M2 phenotype in vitro and increased M2 macrophage numbers in EAP prostates.
Conclusions:
- MS-275 effectively suppresses inflammatory reactions in EAP by modulating immune cell responses and inflammatory mediators.
- The drug promotes the induction of anti-inflammatory immune cells and molecules.
- MS-275 shows promise as a potential therapeutic agent for inflammatory prostatitis.
