{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T06:01:59Z","timestamp":1778997719683,"version":"3.51.4"},"reference-count":24,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2022R1I1A1A01053007"],"award-info":[{"award-number":["NRF-2022R1I1A1A01053007"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2022R1F1A1074769"],"award-info":[{"award-number":["NRF-2022R1F1A1074769"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2022R1I1A1A01053007"],"award-info":[{"award-number":["NRF-2022R1I1A1A01053007"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2022R1F1A1074769"],"award-info":[{"award-number":["NRF-2022R1F1A1074769"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Microglia, essential immune cells in the brain, play crucial roles in neuroinflammation by performing various functions such as neurogenesis, synaptic pruning, and pathogen defense. These cells are activated by inflammatory factors like \u03b2-amyloid (A\u03b2) and oxysterols, leading to morphological and functional changes, including the secretion of inflammatory cytokines and the upregulation of MHC class II molecules. This study focused on identifying specific markers for microglial activation, with a particular emphasis on the roles of oxysterols in this process. We used the HMC3 human microglial cell line to investigate the induction of heat shock protein 60 (HSP60), a chaperonin protein by oxysterols, specifically in the presence of 25-hydroxycholesterol (25OHChol) and 27-hydroxycholesterol (27OHChol). Our findings obtained by the proteomics approach revealed that these oxysterols significantly increased HSP60 expression on microglial cells. This induction was further confirmed using Western blot analysis and immunofluorescence microscopy. Additionally, A\u03b21\u201342 also promoted HSP60 expression, indicating its role as a microglial activator. HSP60 involved in protein folding and immune modulation was identified as a potential marker for microglial activation. This study underscores the importance of HSP60 in the inflammatory response of microglia, suggesting its utility as a target for new therapeutic approaches in neuroinflammatory diseases such as Alzheimer\u2019s disease (AD).<\/jats:p>","DOI":"10.3390\/ijms25169073","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T05:16:24Z","timestamp":1724649384000},"page":"9073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Oxysterol Induces Expression of 60 kDa Chaperone Protein on Cell Surface of Microglia"],"prefix":"10.3390","volume":"25","author":[{"given":"Koanhoi","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-0645","authenticated-orcid":false,"given":"Hyok-rae","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine, Kosin University, Busan 49267, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3327-2730","authenticated-orcid":false,"given":"Bo-young","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaesung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongha","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7757-7412","authenticated-orcid":false,"given":"Ryuk Jun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Family Medicine Clinic and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"},{"name":"Department of Family Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3256-8509","authenticated-orcid":false,"given":"Yonghae","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/glia.20928","article-title":"Innate immunity and neuroinflammation in the CNS: The role of microglia in Toll-like receptor-mediated neuronal injury","volume":"58","author":"Lehnardt","year":"2009","journal-title":"Glia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.devcel.2015.01.018","article-title":"Microglia: Multitasking Specialists of the Brain","volume":"32","author":"Casano","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.2174\/092986707780597961","article-title":"Microglial Activation and its Implications in the Brain Diseases","volume":"14","author":"Kaur","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/jnr.20562","article-title":"Microglia in health and disease","volume":"81","author":"Kim","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1742-2094-1-14","article-title":"Microglia and neuroinflammation: A pathological perspective","volume":"1","author":"Streit","year":"2004","journal-title":"J. Neuroinflamm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0022-510X(87)90218-8","article-title":"Microglia are the major cell type expressing MHC class II in human white matter","volume":"80","author":"Hayes","year":"1987","journal-title":"J. Neurol. Sci."},{"key":"ref_7","first-page":"136","article-title":"Role of pro-inflammatory cytokines released from microglia in Alzheimer\u2019s disease","volume":"3","author":"Wang","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1002\/eji.201847540","article-title":"Microglial MHC class II is dispensable for experimental autoimmune encephalomyelitis and cuprizone-induced demyelination","volume":"48","author":"Wolf","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1161\/01.ATV.0000013312.32196.49","article-title":"Oxysterols","volume":"22","author":"Bjorkhem","year":"2002","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jsbmb.2019.03.003","article-title":"Alterations in cholesterol metabolism as a risk factor for developing Alzheimer\u2019s disease: Potential novel targets for treatment","volume":"190","author":"Goikolea","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.redox.2016.09.001","article-title":"Changes in brain oxysterols at different stages of Alzheimer\u2019s disease: Their involvement in neuroinflammation","volume":"10","author":"Testa","year":"2016","journal-title":"Redox Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10666","DOI":"10.1073\/pnas.1404271111","article-title":"25-Hydroxycholesterol acts as an amplifier of inflammatory signaling","volume":"111","author":"Gold","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.taap.2013.12.007","article-title":"27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5-expressing Th1 lymphocytes","volume":"274","author":"Kim","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.bbrc.2013.07.046","article-title":"Oxysterols induce transition of monocytic cells to phenotypically mature dendritic cell-like cells","volume":"438","author":"Son","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Son, Y., Yeo, I.-J., Hong, J.-T., Eo, S.-K., Lee, D., and Kim, K. (2023). Side-Chain Immune Oxysterols Induce Neuroinflammation by Activating Microglia. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015288"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12974-018-1214-5","article-title":"HSP60 critically regulates endogenous IL-1\u03b2 production in activated microglia by stimulating NLRP3 inflammasome pathway","volume":"15","author":"Swaroop","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0486-x","article-title":"HSP60 plays a regulatory role in IL-1\u03b2-induced microglial inflammation via TLR4-p38 MAPK axis","volume":"13","author":"Swaroop","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_18","first-page":"3","article-title":"Heat shock proteins hsp60 and hsp70: Their roles in folding, assembly and membrane translocation of proteins","volume":"167","author":"Langer","year":"1991","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.canlet.2015.02.026","article-title":"The role of heat shock proteins in cancer","volume":"360","author":"Lianos","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105453","DOI":"10.1016\/j.neuint.2022.105453","article-title":"Potential application of heat shock proteins as therapeutic targets in Parkinson\u2019s disease","volume":"162","author":"Guo","year":"2023","journal-title":"Neurochem. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/mp.2017.246","article-title":"Markers of microglia in post-mortem brain samples from patients with Alzheimer\u2019s disease: A systematic review","volume":"23","author":"Hopperton","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lier, J., Streit, W.J., and Bechmann, I. (2021). Beyond Activation: Characterizing Microglial Functional Phenotypes. Cells, 10.","DOI":"10.3390\/cells10092236"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jsbmb.2017.04.015","article-title":"27-Hydroxycholesterol upregulates the production of heat shock protein 60 of monocytic cells","volume":"172","author":"Kim","year":"2017","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Son, H., Choi, H.-S., Baek, S.E., Kim, Y.-H., Hur, J., Han, J.-H., Moon, J.H., Lee, G.S., Park, S.G., and Woo, C.-H. (2023). Shear stress induces monocyte\/macrophage-mediated inflammation by upregulating cell-surface expression of heat shock proteins. Biomed. Pharmacother., 161.","DOI":"10.1016\/j.biopha.2023.114566"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/9073\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:40:33Z","timestamp":1760110833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/9073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,21]]},"references-count":24,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25169073"],"URL":"https:\/\/doi.org\/10.3390\/ijms25169073","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,21]]}}}