{"title":"泛素特异性肽酶8通过靶向RIPK2泛素化对感染性骨髓炎的发病至关重要。","authors":"Yuanliang Chen, Yongbai Wan, Haojie Shan, Yiwei Lin, Wenyang Xia, Fuli Yin, Chaolai Jiang, Zhongmin Shi","doi":"10.7883/yoken.JJID.2022.515","DOIUrl":null,"url":null,"abstract":"<p><p>Receptor-interacting serine/threonine kinase (RIPK) is associated with cellular inflammation and immune regulation. The current study explored the role of RIPK2 in osteomyelitis and the potential upstream targets of RIPK2. A Staphylococcus aureus-induced osteomyelitis mouse model was established using wild-type (WT) and ubiquitin-specific peptidase 8 (USP8)-deficient (USP<sup>-/-</sup>) mice, and the osteomyelitis-related symptoms were evaluated. Bone marrow-derived macrophages (BMDMs) were isolated from the WT and USP<sup>-/-</sup> mice. Enzyme-linked immunosorbent assays, quantitative polymerase chain reaction, and immunoblot analysis were used to determine the levels of target biomarkers, which were induced by lipopolysaccharide (LPS), CpG, or PAM3CSK4. USP8 promoted RIPK2-mediated NF-κB activation. USP8 is indispensable for RIPK2-mediated LPS-induced NF-κB activation in BMDMs. USP8 is required for the production of inflammatory cytokines induced by LPS, CpG, or PAM3CSK4 in BMDMs. In addition, USP<sup>-/-</sup> mice exhibited ameliorated symptoms, including less body weight and cortical bone loss, and reduced bacterial load and reactive bone formation in the S. aureus-induced osteomyelitis mouse model. USP8 is critical in the S. aureus-induced osteomyelitis mouse model by targeting RIPK2 ubiquitination.</p>","PeriodicalId":14608,"journal":{"name":"Japanese journal of infectious diseases","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ubiquitin-Specific Peptidase 8 Is Critical for the Onset of Infectious Osteomyelitis by Targeting RIPK2 Ubiquitination.\",\"authors\":\"Yuanliang Chen, Yongbai Wan, Haojie Shan, Yiwei Lin, Wenyang Xia, Fuli Yin, Chaolai Jiang, Zhongmin Shi\",\"doi\":\"10.7883/yoken.JJID.2022.515\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Receptor-interacting serine/threonine kinase (RIPK) is associated with cellular inflammation and immune regulation. The current study explored the role of RIPK2 in osteomyelitis and the potential upstream targets of RIPK2. A Staphylococcus aureus-induced osteomyelitis mouse model was established using wild-type (WT) and ubiquitin-specific peptidase 8 (USP8)-deficient (USP<sup>-/-</sup>) mice, and the osteomyelitis-related symptoms were evaluated. Bone marrow-derived macrophages (BMDMs) were isolated from the WT and USP<sup>-/-</sup> mice. Enzyme-linked immunosorbent assays, quantitative polymerase chain reaction, and immunoblot analysis were used to determine the levels of target biomarkers, which were induced by lipopolysaccharide (LPS), CpG, or PAM3CSK4. USP8 promoted RIPK2-mediated NF-κB activation. USP8 is indispensable for RIPK2-mediated LPS-induced NF-κB activation in BMDMs. USP8 is required for the production of inflammatory cytokines induced by LPS, CpG, or PAM3CSK4 in BMDMs. In addition, USP<sup>-/-</sup> mice exhibited ameliorated symptoms, including less body weight and cortical bone loss, and reduced bacterial load and reactive bone formation in the S. aureus-induced osteomyelitis mouse model. USP8 is critical in the S. aureus-induced osteomyelitis mouse model by targeting RIPK2 ubiquitination.</p>\",\"PeriodicalId\":14608,\"journal\":{\"name\":\"Japanese journal of infectious diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2023-05-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Japanese journal of infectious diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7883/yoken.JJID.2022.515\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Japanese journal of infectious diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7883/yoken.JJID.2022.515","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Ubiquitin-Specific Peptidase 8 Is Critical for the Onset of Infectious Osteomyelitis by Targeting RIPK2 Ubiquitination.
Receptor-interacting serine/threonine kinase (RIPK) is associated with cellular inflammation and immune regulation. The current study explored the role of RIPK2 in osteomyelitis and the potential upstream targets of RIPK2. A Staphylococcus aureus-induced osteomyelitis mouse model was established using wild-type (WT) and ubiquitin-specific peptidase 8 (USP8)-deficient (USP-/-) mice, and the osteomyelitis-related symptoms were evaluated. Bone marrow-derived macrophages (BMDMs) were isolated from the WT and USP-/- mice. Enzyme-linked immunosorbent assays, quantitative polymerase chain reaction, and immunoblot analysis were used to determine the levels of target biomarkers, which were induced by lipopolysaccharide (LPS), CpG, or PAM3CSK4. USP8 promoted RIPK2-mediated NF-κB activation. USP8 is indispensable for RIPK2-mediated LPS-induced NF-κB activation in BMDMs. USP8 is required for the production of inflammatory cytokines induced by LPS, CpG, or PAM3CSK4 in BMDMs. In addition, USP-/- mice exhibited ameliorated symptoms, including less body weight and cortical bone loss, and reduced bacterial load and reactive bone formation in the S. aureus-induced osteomyelitis mouse model. USP8 is critical in the S. aureus-induced osteomyelitis mouse model by targeting RIPK2 ubiquitination.
期刊介绍:
Japanese Journal of Infectious Diseases (JJID), an official bimonthly publication of National Institute of Infectious Diseases, Japan, publishes papers dealing with basic research on infectious diseases relevant to humans in the fields of bacteriology, virology, mycology, parasitology, medical entomology, vaccinology, and toxinology. Pathology, immunology, biochemistry, and blood safety related to microbial pathogens are among the fields covered. Sections include: original papers, short communications, epidemiological reports, methods, laboratory and epidemiology communications, letters to the editor, and reviews.