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However, approximately 5% of patients continue to have inflammatory symptoms even after receiving antibacterial therapy, leading to refractory conditions. Bacterial prostatitis requires additional therapy, focusing on inflammatory changes. Indoleamine 2,3-dioxygenase 1 (IDO1) catalysis is the first rate-limiting step of tryptophan metabolism. IDO1 is expressed in the prostate and plays a key role in the immune response. As the first step in investigating the relationship between acute prostatitis and IDO1, we investigated the preventive effect of IDO1 inhibition on lipopolysaccharide (LPS)- induced prostatitis using IDO knockout (Ido1 −/−) mice in this study.\n Materials and Methods: The study used Ido1 −/− and wild-type (Ido1 +/+) C57BL/6J male\nmice aged 10–15 weeks. LPS Escherichia coli O26 (100μg/PBS, 100μL) was administered transurethrally into the lower urinary tract to create a mouse model of LPS-induced prostatitis. The prostates were removed 1, 3, 5, and 7 days after creating the model mice. Histological, immunohistochemical, and biochemical analyses were used to compare the preventive effect in Ido1 −/− mice compared with that in Ido1+/+ mice.\n Results: HE staining showed suppression of ductal destruction following infiltration of inflammatory cells in Ido1 −/− mice compared with Ido1 +/+ mice. The enzyme-linked immunosorbent assay (ELISA) method was used for kynurenine pathway analysis, which showed significantly maintained tryptophan levels and decreased L-kynurenine levels in Ido1 −/− mice compared to Ido1 +/+ mice. The IDO1 assay in Ido1 +/+ mice showed significantly increased levels during all observation periods after creating the model compared with that under normal conditions. Immunofluorescent staining using five types of cytokines and chemokines (IL-2, IL-4, IL-17, CCL2, and CCL3) related to the pathophysiology of acute prostatitis showed decreased expression of these cytokines and chemokines in Ido1 -/- mice compared with Ido1 +/+ mice. Inflammation-related proteome assays showed decreased levels of IL-1β, IL-4, IL-5, IL-6, IL-17, CCL2, CCL3, CXCL1, CXCL11, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 in Ido1 −/− mice compared with Ido1 −/− mice during all observation periods after model creation.\n Conclusions: IDO1 is involved in LPS-induced prostatitis through cytokines and chemokines. IDO1 inhibition contributes to the prevention of LPS-induced prostatitis. 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Preventive effect of indoleamine 2,3-dioxygenase 1 inhibition on lipopolysaccharide-induced prostatitis
https://kwmed.repo.nii.ac.jp/records/3062
https://kwmed.repo.nii.ac.jp/records/30627cfa2133-6a0f-40c9-8c2e-109dde4c7fa3
名前 / ファイル | ライセンス | アクション |
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PDF (4.8 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2023-03-10 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Preventive effect of indoleamine 2,3-dioxygenase 1 inhibition on lipopolysaccharide-induced prostatitis | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
TAKASAKI, Hiroyasu
× TAKASAKI, Hiroyasu× OHIRA, Shin× TONE, Shigenobu× KAKUMAE, Sho× NAKATSUKA, Tota× MORINAKA, Hirofumi× HIRATA, Keita× SHIMIZU, Shinjiro× NAGAI, Atsushi× UEHARA, Shinya \n |
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著者所属(英) | ||||||
en | ||||||
Department of Urology, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Department of Urology, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Faculty of Science and Engineering, Tokyo Denki University | ||||||
著者所属(英) | ||||||
en | ||||||
Department of Urology, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Department of Urology, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Department of Urology, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Department of Urology, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Department of Urology, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Director of Hospital, Kawasaki Medical School Hospital | ||||||
著者所属(英) | ||||||
en | ||||||
Department of Urology, Kawasaki Medical School | ||||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Indoleamine 2,3-dioxygenase 1 | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Prostatitis | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Prevention | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Anti-inflammation | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | lipopolysaccharide | |||||
抄録(英) | ||||||
en | ||||||
Introduction and Objectives: Bacterial infections are the main cause of acute prostatitis and are treated with appropriate antimicrobial therapy. However, approximately 5% of patients continue to have inflammatory symptoms even after receiving antibacterial therapy, leading to refractory conditions. Bacterial prostatitis requires additional therapy, focusing on inflammatory changes. Indoleamine 2,3-dioxygenase 1 (IDO1) catalysis is the first rate-limiting step of tryptophan metabolism. IDO1 is expressed in the prostate and plays a key role in the immune response. As the first step in investigating the relationship between acute prostatitis and IDO1, we investigated the preventive effect of IDO1 inhibition on lipopolysaccharide (LPS)- induced prostatitis using IDO knockout (Ido1 −/−) mice in this study. Materials and Methods: The study used Ido1 −/− and wild-type (Ido1 +/+) C57BL/6J male mice aged 10–15 weeks. LPS Escherichia coli O26 (100μg/PBS, 100μL) was administered transurethrally into the lower urinary tract to create a mouse model of LPS-induced prostatitis. The prostates were removed 1, 3, 5, and 7 days after creating the model mice. Histological, immunohistochemical, and biochemical analyses were used to compare the preventive effect in Ido1 −/− mice compared with that in Ido1+/+ mice. Results: HE staining showed suppression of ductal destruction following infiltration of inflammatory cells in Ido1 −/− mice compared with Ido1 +/+ mice. The enzyme-linked immunosorbent assay (ELISA) method was used for kynurenine pathway analysis, which showed significantly maintained tryptophan levels and decreased L-kynurenine levels in Ido1 −/− mice compared to Ido1 +/+ mice. The IDO1 assay in Ido1 +/+ mice showed significantly increased levels during all observation periods after creating the model compared with that under normal conditions. Immunofluorescent staining using five types of cytokines and chemokines (IL-2, IL-4, IL-17, CCL2, and CCL3) related to the pathophysiology of acute prostatitis showed decreased expression of these cytokines and chemokines in Ido1 -/- mice compared with Ido1 +/+ mice. Inflammation-related proteome assays showed decreased levels of IL-1β, IL-4, IL-5, IL-6, IL-17, CCL2, CCL3, CXCL1, CXCL11, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 in Ido1 −/− mice compared with Ido1 −/− mice during all observation periods after model creation. Conclusions: IDO1 is involved in LPS-induced prostatitis through cytokines and chemokines. IDO1 inhibition contributes to the prevention of LPS-induced prostatitis. IDO1 inhibition has the potential to serve as an additional therapy for acute prostatitis. |
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書誌情報 |
en : Kawasaki medical journal 巻 48, p. 141-151, 発行日 2022 |
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出版者 | ||||||
出版者 | Kawasaki Medical Society | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 24343404 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA12029005 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.11482/KMJ-E202248141 | |||||
記事種別(英) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Regular Article | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://igakkai.kms-igakkai.com/wp/wp-content/uploads/2022en/KMJ-E202248141.pdf | |||||
関連名称 | https://igakkai.kms-igakkai.com/wp/wp-content/uploads/2022en/KMJ-E202248141.pdf | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |