• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

活化蛋白-1激活KCNN4介导的钙信号传导，以诱导慢性非细菌性前列腺炎中CD4细胞向Th1/Th17分化。

AP-1 activates KCNN4-mediated Ca2 signaling to induce the Th1/Th17 differentiation of CD4 cells in chronic non-bacterial prostatitis.

作者信息

Teng Jingfei, Jia Zhuomin, Gao Feng, Guan Yawei, Yao Li, Ma Chong, Li Zhihui, Ai Xing

机构信息

Department of Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, P.R. China.

Department of Urology, The Third Medical Center of Chinese PLA General Hospital, Beijing, 100039, P.R. China.

出版信息

Cell Biol Toxicol. 2024 Dec 27;41(1):18. doi: 10.1007/s10565-024-09967-1.

DOI:10.1007/s10565-024-09967-1
PMID:39729199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11680619/
Abstract

The intraprostatic inflammatory infiltrate is characterized by Th1 CD4 T cells, and its molecular mechanism is not well defined. This study explored the mechanisms responsible for the alteration of Th1/Th17 differentiation of CD4 T cells in chronic non-bacterial prostatitis (CNP). CNP rats were induced by the administration of testosterone and 17β-estradiol. The Th1/Th17 cell percentage was increased in the prostate tissue of CNP rats, which was accompanied by increased IL-2, IFN-γ, IL-17A, and IL-22 levels. Transcriptome sequencing was performed, followed by KEGG pathway enrichment analysis. Activator protein-1 (AP-1) was enhanced in CD4 T cells from CNP rats, and its inhibitor SR11302 suppressed Th1/Th17 differentiation and delayed CNP. AP-1 transcriptionally activated the expression of KCNN4, which potentiated mTORC1 in CD4 T cells by enhancing Ca2 signaling, thereby promoting Th1/Th17 differentiation. Rapamycin-mediated autophagy activation reversed AP-1/KCNN4/mTORC1-promoted Th1/Th17 differentiation, thereby inhibiting CNP. These results suggest that AP-1-mediated KCNN4 transcription promotes the inhibition of autophagy by mTORC1 through Ca2 signaling, which supports Th1/Th17 differentiation of CD4 T cells, resulting in the transformation of CNP to prostatic intraepithelial neoplasia and adenocarcinoma.

摘要

前列腺内的炎性浸润以Th1 CD4 T细胞为特征，其分子机制尚不清楚。本研究探讨了慢性非细菌性前列腺炎（CNP）中CD4 T细胞Th1/Th17分化改变的机制。通过给予睾酮和17β-雌二醇诱导建立CNP大鼠模型。CNP大鼠前列腺组织中Th1/Th17细胞百分比增加，同时伴有IL-2、IFN-γ、IL-17A和IL-22水平升高。进行转录组测序，随后进行KEGG通路富集分析。在CNP大鼠的CD4 T细胞中激活蛋白-1（AP-1）增强，其抑制剂SR11302抑制Th1/Th17分化并延缓CNP进展。AP-1转录激活KCNN4的表达，通过增强Ca2信号增强CD4 T细胞中的mTORC1，从而促进Th1/Th17分化。雷帕霉素介导的自噬激活逆转了AP-1/KCNN4/mTORC1促进的Th1/Th17分化，从而抑制CNP。这些结果表明，AP-1介导的KCNN4转录通过Ca2信号促进mTORC1对自噬的抑制，支持CD4 T细胞的Th1/Th17分化，导致CNP转变为前列腺上皮内瘤变和腺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/679d4605b7b9/10565_2024_9967_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/95afc359f50f/10565_2024_9967_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/7d8bd6eb2453/10565_2024_9967_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/52d1818192ad/10565_2024_9967_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/2d63e94f25d0/10565_2024_9967_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/4f733c77fdbf/10565_2024_9967_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/11b2c403b03e/10565_2024_9967_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/bf55e3374620/10565_2024_9967_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/679d4605b7b9/10565_2024_9967_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/95afc359f50f/10565_2024_9967_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/7d8bd6eb2453/10565_2024_9967_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/52d1818192ad/10565_2024_9967_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/2d63e94f25d0/10565_2024_9967_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/4f733c77fdbf/10565_2024_9967_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/11b2c403b03e/10565_2024_9967_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/bf55e3374620/10565_2024_9967_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cb/11680619/679d4605b7b9/10565_2024_9967_Fig8_HTML.jpg

相似文献

1
AP-1 activates KCNN4-mediated Ca2 signaling to induce the Th1/Th17 differentiation of CD4 cells in chronic non-bacterial prostatitis.活化蛋白-1激活KCNN4介导的钙信号传导，以诱导慢性非细菌性前列腺炎中CD4细胞向Th1/Th17分化。
Cell Biol Toxicol. 2024 Dec 27;41(1):18. doi: 10.1007/s10565-024-09967-1.
2
Qingchang suppository ameliorates mucosal inflammation in ulcerative colitis by inhibiting the differentiation and effector functions of Th1 and Th17 cells.清肠栓通过抑制 Th1 和 Th17 细胞的分化和效应功能来改善溃疡性结肠炎的黏膜炎症。
J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118865. doi: 10.1016/j.jep.2024.118865. Epub 2024 Sep 28.
3
Role of ITK signaling in acute kidney injury in mice: Amelioration of acute kidney injury associated clinical parameters and attenuation of inflammatory transcription factor signaling in CD4+ T cells by ITK inhibition.ITK 信号在小鼠急性肾损伤中的作用：通过 ITK 抑制改善急性肾损伤相关临床参数，并减弱 CD4+T 细胞中炎症转录因子信号。
Int Immunopharmacol. 2021 Oct;99:108028. doi: 10.1016/j.intimp.2021.108028. Epub 2021 Aug 5.
4
IL-25 downregulates Th1/Th17 immune response in an IL-10-dependent manner in inflammatory bowel disease.白细胞介素-25 通过依赖白细胞介素-10 的方式下调炎症性肠病中的 Th1/Th17 免疫应答。
Inflamm Bowel Dis. 2013 Mar-Apr;19(4):720-8. doi: 10.1097/MIB.0b013e3182802a76.
5
mTOR-Myc axis drives acinar-to-dendritic cell transition and the CD4 T cell immune response in acute pancreatitis.mTOR-Myc 轴驱动急性胰腺炎中腺泡细胞向树突状细胞的转化和 CD4 T 细胞免疫应答。
Cell Death Dis. 2020 Jun 2;11(6):416. doi: 10.1038/s41419-020-2517-x.
6
BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis.BJ-1108，一种6-氨基-2,4,5-三甲基吡啶-3-醇类似物，可调节Th1和Th17细胞的分化以改善实验性自身免疫性脑脊髓炎。
Biol Res. 2017 Feb 28;50(1):8. doi: 10.1186/s40659-017-0113-z.
7
Erythromycin Prevents Elastin Peptide-Induced Emphysema and Modulates CD4T Cell Responses in Mice.红霉素可预防弹性蛋白肽诱导的小鼠肺气肿并调节 CD4 T 细胞反应。
Int J Chron Obstruct Pulmon Dis. 2019 Nov 29;14:2697-2709. doi: 10.2147/COPD.S222195. eCollection 2019.
8
Regulatory effect of nicotine on the differentiation of Th1, Th2 and Th17 lymphocyte subsets in patients with rheumatoid arthritis.尼古丁对类风湿关节炎患者 Th1、Th2 和 Th17 淋巴细胞亚群分化的调节作用。
Eur J Pharmacol. 2018 Jul 15;831:38-45. doi: 10.1016/j.ejphar.2018.04.028. Epub 2018 Apr 30.
9
Oxidative stress modulates the cytokine response of differentiated Th17 and Th1 cells.氧化应激调节分化的Th17细胞和Th1细胞的细胞因子反应。
Free Radic Biol Med. 2016 Oct;99:352-363. doi: 10.1016/j.freeradbiomed.2016.08.026. Epub 2016 Aug 24.
10
IL-7/IL-7 Receptor Signaling Differentially Affects Effector CD4+ T Cell Subsets Involved in Experimental Autoimmune Encephalomyelitis.白细胞介素-7/白细胞介素-7受体信号传导对实验性自身免疫性脑脊髓炎中效应性CD4 + T细胞亚群有不同影响。
J Immunol. 2015 Sep 1;195(5):1974-83. doi: 10.4049/jimmunol.1403135. Epub 2015 Jul 29.

本文引用的文献

1
Chronic prostatitis (chronic pelvic pain syndrome).慢性前列腺炎（慢性盆腔疼痛综合征）。
BMJ. 2023 Nov 17;383:e073908. doi: 10.1136/bmj-2023-073908.
2
Preclinical models and evaluation criteria of prostatitis.前列腺炎的临床前模型和评价标准。
Front Immunol. 2023 May 9;14:1183895. doi: 10.3389/fimmu.2023.1183895. eCollection 2023.
3
Morin, the PPARγ agonist, inhibits Th17 differentiation by limiting fatty acid synthesis in collagen-induced arthritis.莫林，过氧化物酶体增殖物激活受体γ 激动剂，通过限制胶原诱导性关节炎中的脂肪酸合成来抑制 Th17 分化。
Cell Biol Toxicol. 2023 Aug;39(4):1433-1452. doi: 10.1007/s10565-022-09769-3. Epub 2022 Sep 19.
4
Celastrol inhibits LL37-induced rosacea by inhibiting Ca/CaMKII-mTOR-NF-κB activation.藜芦碱通过抑制 Ca/CaMKII-mTOR-NF-κB 激活抑制 LL37 诱导的酒渣鼻。
Biomed Pharmacother. 2022 Sep;153:113292. doi: 10.1016/j.biopha.2022.113292. Epub 2022 Jun 16.
5
Channelopathy of small- and intermediate-conductance Ca-activated K channels.小电导和中等电导钙激活钾通道的通道病。
Acta Pharmacol Sin. 2023 Feb;44(2):259-267. doi: 10.1038/s41401-022-00935-1. Epub 2022 Jun 17.
6
Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets.染色质特征可对去势抵抗性前列腺癌进行分类，提示治疗靶点。
Science. 2022 May 27;376(6596):eabe1505. doi: 10.1126/science.abe1505.
7
Impact of STAT Proteins in Tumor Progress and Therapy Resistance in Advanced and Metastasized Prostate Cancer.信号转导和转录激活因子（STAT）蛋白在晚期和转移性前列腺癌肿瘤进展及治疗耐药中的作用
Cancers (Basel). 2021 Sep 28;13(19):4854. doi: 10.3390/cancers13194854.
8
Chronic Prostatitis and Pelvic Pain Syndrome: Another Autoimmune Disease?慢性前列腺炎和盆腔疼痛综合征：另一种自身免疫性疾病？
Arch Immunol Ther Exp (Warsz). 2021 Sep 14;69(1):24. doi: 10.1007/s00005-021-00628-3.
9
RpfE-Induced Prostaglandin E2 in Dendritic Cells Induces Th1/Th17 Cell Differentiation.树突状细胞中 RpfE 诱导的前列腺素 E2 诱导 Th1/Th17 细胞分化。
Int J Mol Sci. 2021 Jul 14;22(14):7535. doi: 10.3390/ijms22147535.
10
The mTOR-Autophagy Axis and the Control of Metabolism.mTOR-自噬轴与代谢调控
Front Cell Dev Biol. 2021 Jul 1;9:655731. doi: 10.3389/fcell.2021.655731. eCollection 2021.