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

IF 1.5 Q3 UROLOGY & NEPHROLOGY
American journal of clinical and experimental urology Pub Date : 2024-08-25 eCollection Date: 2024-01-01 DOI:10.62347/PEGK4888
Robbie Sj Manuel, Allison Rundquist, Marcela Ambrogi, Brandon R Scharpf, Nelson T Peterson, Jaskiran K Sandhu, Sneha Chandrashekar, Monica Ridlon, Latasha K Crawford, Kimberly P Keil-Stietz, Richard E Peterson, Chad M Vezina
{"title":"The aryl hydrocarbon receptor agonist ITE reduces inflammation and urinary dysfunction in a mouse model of autoimmune prostatitis.","authors":"Robbie Sj Manuel, Allison Rundquist, Marcela Ambrogi, Brandon R Scharpf, Nelson T Peterson, Jaskiran K Sandhu, Sneha Chandrashekar, Monica Ridlon, Latasha K Crawford, Kimberly P Keil-Stietz, Richard E Peterson, Chad M Vezina","doi":"10.62347/PEGK4888","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>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).</p><p><strong>Methods: </strong>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 <i>in situ</i> RNA detection.</p><p><strong>Results: </strong>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 <i>H2-Ab1</i>, <i>S100a8</i>, and <i>S100a9</i>. ITE also increased the abundance of the AHR-responsive <i>Cyp1a1</i> RNA.</p><p><strong>Conclusions: </strong>These findings support the hypothesis that ITE activates the AHR in the prostate and reduces autoimmune-mediated prostatitis in mice.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411176/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of clinical and experimental urology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.62347/PEGK4888","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

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.

芳基烃受体激动剂 ITE 能减轻自身免疫性前列腺炎小鼠模型的炎症和排尿功能障碍。
目的:前列腺炎症与下尿路功能障碍有关,是慢性前列腺炎/慢性盆腔疼痛综合征的关键因素。最近发现,自身免疫是前列腺炎症的一个驱动因素。芳基烃受体(AHR)是一种配体激活的转录因子,它的激动剂已被用于抑制小鼠结肠炎、鼻炎和皮炎模型中的自身免疫,但 AHR 激动剂是否能抑制前列腺自身免疫还没有被研究过。在此,我们测试了 AHR 激动剂 ITE(2-(1'H-吲哚-3'-羰基)-噻唑-4-羧酸甲酯)是否能抑制实验性自身免疫性前列腺炎(EAP)小鼠模型中的炎症、异动症和排尿功能障碍:方法:用大鼠前列腺抗原或 TiterMax Gold® 佐剂(无炎症对照)免疫 C57BL/6J 成年雄性小鼠,诱导 EAP。小鼠还接受 ITE(10 毫克/千克/天 IP)或 DMSO(载体,5 毫克/千克/天 IP)治疗 6 天。我们使用 Nanostring nCounter Inflammation Panel 评估了 EAP 和 ITE 对前列腺 RNA 丰度的影响。我们通过 RT-PCR 和 RNAScope 原位 RNA 检测验证了 EAP 和 ITE 介导的一组 RNA 的变化:结果:EAP似乎加剧了前列腺背侧的组织学炎症,诱发了触觉过敏,并似乎增加了非排尿性膀胱收缩的频率。ITE 可减轻 EAP 的某些作用。EAP 改变了 40 种炎症相关 RNA 的丰度,而 ITE 则改变了 28 种炎症相关 RNA 的丰度。我们确定了一组 RNA,其中 ITE 可防止 EAP 引起的 H2-Ab1、S100a8 和 S100a9 的丰度变化。ITE 还增加了 AHR 反应性 Cyp1a1 RNA 的丰度:这些发现支持了 ITE 可激活前列腺中的 AHR 并减轻小鼠自身免疫介导的前列腺炎的假设。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
8.30%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信