The aryl hydrocarbon receptor agonist ITE reduces inflammation and urinary dysfunction in a mouse model of autoimmune prostatitis.

Autor:	Manuel RS; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA.; Molecular and Environmental Toxicology Graduate Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA.; Endocrinology and Reproductive Physiology Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA., Rundquist A; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA.; Endocrinology and Reproductive Physiology Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA., Ambrogi M; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA.; Endocrinology and Reproductive Physiology Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA., Scharpf BR; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA.; Molecular and Environmental Toxicology Graduate Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA., Peterson NT; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA.; Molecular and Environmental Toxicology Graduate Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA., Sandhu JK; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA., Chandrashekar S; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA., Ridlon M; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA.; Molecular and Environmental Toxicology Graduate Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA., Crawford LK; Department of Pathological Sciences, University of Wisconsin Madison School of Veterinary Medicine Madison, WI, USA., Keil-Stietz KP; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA.; Molecular and Environmental Toxicology Graduate Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA.; Endocrinology and Reproductive Physiology Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA., Peterson RE; Division of Pharmaceutical Sciences, University of Wisconsin School of Pharmacy Madison, WI, USA., Vezina CM; Department of Comparative Biosciences, University of Wisconsin-Madison Madison, WI, USA.; Molecular and Environmental Toxicology Graduate Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA.; Endocrinology and Reproductive Physiology Program, University of Wisconsin School of Medicine and Public Health Madison, WI, USA.
Jazyk:	angličtina
Zdroj:	American journal of clinical and experimental urology [Am J Clin Exp Urol] 2024 Aug 25; Vol. 12 (4), pp. 149-161. Date of Electronic Publication: 2024 Aug 25 (Print Publication: 2024).
DOI:	10.62347/PEGK4888
Abstrakt:	Objectives: Prostate inflammation is linked to lower urinary tract dysfunction and is a key factor in chronic prostatitis/chronic pelvic pain syndrome. Autoimmunity was recently identified as a driver of prostate inflammation. Agonists of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, have been used to suppress autoimmunity in mouse models of colitis, rhinitis, and dermatitis, but whether AHR agonists suppress prostate autoimmunity has not been examined. Here, we test whether ITE (2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester), an AHR agonist, suppresses inflammation, allodynia, and urinary dysfunction in a mouse model of experimental autoimmune prostatitis (EAP). Methods: C57BL/6J adult male mice were immunized with rat prostate antigen to induce EAP or TiterMax Gold® adjuvant (uninflamed control). Mice were also treated with ITE (10 mg/kg/day IP) or DMSO (vehicle, 5 mg/kg/day IP) for 6 days. Using the Nanostring nCounter Inflammation Panel, we evaluated the impact of EAP and ITE on prostatic RNA abundance. We validated EAP and ITE-mediated changes in a subset of RNAs by RT-PCR and RNAScope in situ RNA detection. Results: EAP appeared to heighten histological inflammation in the dorsal prostate, induced tactile allodynia, and appeared to increase the frequency of non-voiding bladder contractions. ITE mitigated some actions of EAP. EAP changed abundance of 40 inflammation-related RNAs, while ITE changed abundance of 28 inflammation-related RNAs. We identified a cluster of RNAs for which ITE protected against EAP-induced changes in the abundance of H2-Ab1 , S100a8 , and S100a9 . ITE also increased the abundance of the AHR-responsive Cyp1a1 RNA. Conclusions: These findings support the hypothesis that ITE activates the AHR in the prostate and reduces autoimmune-mediated prostatitis in mice. Competing Interests: None. (AJCEU Copyright © 2024.)
Databáze:	MEDLINE
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