Role of histone deacetylase type 11 (HDAC11) in the inflammatory modulation of the prostate in LPS-induced prostatitis

• Grant number: 21/14495-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 08, 2022
• End date: May 07, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Autonomic Pharmacology
• Principal Investigator: Fabíola Taufic Monica Iglesias
• Grantee: Ana Carolina Ghezzi Beghini
• Supervisor: Edward Seto
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: George Washington University, United States
• Associated to the scholarship: 19/19490-4 - Role of inhibitors of histone deacetylase and DNA-methyltransferase and activator of sirtuin-1 on the NO-sGC-cGMP pathway in the bladder, urethra and prostate under physiological and pathological conditions (obesity and cystitis)., BP.PD

Abstract

Prostatitis is a pathology characterized by infection and/or inflammation of the prostate gland. Studies have shown that prostatitis has an inflammatory and autoimmune basis. Prostatitis affects men of all ages, with a high impact on middleaged people. The treatment for prostatitis is not well established and most often has low therapeutic efficacy and does not prevent the progression and recurrence of prostatitis. The experimental models used for the study of prostatitis are the intraprostatic or the intraurethral injections of LPS or formalin. An Experimental model of prostatic inflammation induced by bacterial infection produces a significant increase in the frequency of urination with a decrease in urine volume, as well as promotes tissue remodeling and stimulates the pattern of pro-inflammatory cytokines. A study showed an association of chronic prostatitis/chronic pelvic pain syndrome with epigenetic factors. Epigenetic alterations are frequently seen in chronic inflammatory diseases. DNA methylation, post-translational histone modifications (acetylation and deacetylation, for example), and non-coding RNA are the main epigenetic mechanisms that lead to alterations in gene expression. The histone modifying enzyme, HDAC11, plays a key role in the regulation of immune cells, and presents itself as an important target for the treatment of inflammatory diseases. However, a better understanding of the role of HDAC11, as well as its biological effects, on prostatitis require further studies. The aim of this study is to analyze the role of HDAC11 in the modulation of inflammation, chemokines and immune system cells in the prostate of mice with prostatitis. We will use HDAC11 knockout mice with prostatitis induced by intraurethral injection of LPS and their respective control group and evaluate i) the expression of inflammatory cytokines, chemokines, as well as immune system cells infiltrated in the prostate of these animals and ii) the voiding profile. Completion of this work will help elucidate new functions of HDAC11 and its mechanisms of action in prostatitis, and provide insights into future development of therapeutic strategies for prostatitis. (AU)