Indoxyl Sulfate Promotes Macrophage IL-1β Production by Activating Aryl Hydrocarbon Receptor/NF-_K/MAPK Cascades, but the NLRP3 inflammasome Was Not Activated

• Material Type: 博士論文
• Title: Indoxyl Sulfate Promotes Macrophage IL-1β Production by Activating Aryl Hydrocarbon Receptor/NF-_K/MAPK Cascades, but the NLRP3 inflammasome Was Not Activated
• Author/Editor: Wakamatsu, Takuya
• Publication, Distribution, etc.: 新潟大学
• Publication Date: 2018-09-20
• Publication Date (W3CDTF): 2018-09-20
• Alternative Title: Indoxyl Sulfate Promotes Macrophage IL-1β Production by Activating Aryl Hydrocarbon Receptor/NF-_K/MAPK Cascades, but the NLRP3 inflammasome Was Not Activated; インドキシル硫酸は、アリルハイドロカーボン受容体/NF-_K/MAPK経路の活性化を介してIL-1βの発現を亢進させるが、NLRP3インフラマソームを活性化しない。
• Degree grantor/type: 新潟大学
• Date Granted: 2018-09-20
• Date Granted (W3CDTF): 2018-09-20
• Dissertation Number: 甲第4498号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第4498号
• Text Language Code: eng
• Subject Heading: uremic toxins; indoxyl sulfate; macrophage; aryl hydrocarbon receptor; nuclear factor-_KB; inflammasome; atherosclerosis; cardiovascular disease
• Note (General): In chronic kidney disease (CKD) patients, accumulation of uremic toxins is associated with cardiovascular risk and mortality. One of the hallmarks of kidney disease-related cardiovascular disease is intravascular macrophage inflammation, but the mechanism of the reaction with these toxins is not completely understood. Macrophages differentiated from THP-1 cells were exposed to indoxyl sulfate (IS), a representative uremic toxin, and changes in inflammatory cytokine production and intracellular signaling molecules including interleukin (IL)-1, aryl hydrocarbon receptor (AhR), nuclear factor (NF)-_K, and mitogen-activated protein kinase (MAPK) cascades as well as the NLRP3 inflammasome were quantified by real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay. IS induced macrophage pro-IL-1β mRNA expression, although mature IL-1 was only slightly increased. IS increased AhR and the AhR-related mRNA expression; this change was suppressed by administration of proteasome inhibitor. IS promoted phosphorylation of NF-_KB p65 and MAPK enzymes; the reaction and IL-1 expression were inhibited by BAY11-7082, an inhibitor of NF-_KB. In contrast, IS decreased NLRP3 and did not change ASC, pro-caspase 1, or caspase-1 activation. IS-inducing inflammation in macrophages results from accelerating AhR-NF-_KB/MAPK cascades, but the NLRP3 inflammasome was not activated. These reactions may restrict mature IL-1β production, which may explain sustained chronic inflammation in CKD patients.; 学位の種類: 博士（医学）. 報告番号: 甲第4498号. 学位記番号: 新大院博（医）甲第835号. 学位授与年月日: 平成30年9月20日; Toxins. 2018, 10, 124.; 新大院博（医）甲第835号
• DOI: info:doi/10.3390/toxins10030124; https://doi.org/info:doi/10.3390/toxins10030124
• Persistent ID (NDL): info:ndljp/pid/11217068; https://dl.ndl.go.jp/pid/11217068
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2019-01-04T08:16:43+09:00
• Date Created (W3CDTF): 2019-09-10
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10191/50778
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp