BAP1 depletion in human B‐lymphoblast cells affects the production of innate immune cytokines and chemokines
BRCA1 associated protein 1 (BAP1) is a ubiquitin C‐terminal hydrolase that deubiquitinates histone H2AK119ub and other proteins and regulates the expression of multiple genes. The knockout of this tumor suppressor gene results in severe thymic atrophy, complete loss of the T cell lineage, and abnorm...
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| Veröffentlicht in: | Genes to cells : devoted to molecular & cellular mechanisms 2022-12, Vol.27 (12), p.731-740 |
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| creator | Takagi‐Kimura, Misato Tada, Akio Kijima, Takashi Kubo, Shuji Ohmuraya, Masaki Yoshikawa, Yoshie |
| description | BRCA1 associated protein 1 (BAP1) is a ubiquitin C‐terminal hydrolase that deubiquitinates histone H2AK119ub and other proteins and regulates the expression of multiple genes. The knockout of this tumor suppressor gene results in severe thymic atrophy, complete loss of the T cell lineage, and abnormal B cell development in mice. In the current study, we investigated in vitro effects of BAP1 knockout on cytokine and chemokine production using the human B‐lymphoblast cell line TSCE5. We confirmed that knockout changed the production of innate immune‐associated genes and their receptors. The CCL19, CCR7, CCL2, and CXCR5 genes associated with T and B cell migration were upregulated. Knockout cells producing high levels of CCL19 showed acceleration of actin polymerization, which is essential for cell migration. CD69, PTPRC, and TLR3 genes that activate inflammation were downregulated. The tumor necrosis factor ligand genes TNF, LTA, and TNFSF10 were downregulated by knockout. In knockout cells, TNFα production was strongly downregulated upon the addition of H2O2, but NF‐κB in the basal condition and when TNFα was added was augmented, suggesting that these cells could respond to TNFα. These results indicated that BAP1 affects the expression of chemokines and cytokines, T and B cell migration, and activated inflammation associating with innate immunity. |
| doi_str_mv | 10.1111/gtc.12988 |
| format | Article |
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The knockout of this tumor suppressor gene results in severe thymic atrophy, complete loss of the T cell lineage, and abnormal B cell development in mice. In the current study, we investigated in vitro effects of BAP1 knockout on cytokine and chemokine production using the human B‐lymphoblast cell line TSCE5. We confirmed that knockout changed the production of innate immune‐associated genes and their receptors. The CCL19, CCR7, CCL2, and CXCR5 genes associated with T and B cell migration were upregulated. Knockout cells producing high levels of CCL19 showed acceleration of actin polymerization, which is essential for cell migration. CD69, PTPRC, and TLR3 genes that activate inflammation were downregulated. The tumor necrosis factor ligand genes TNF, LTA, and TNFSF10 were downregulated by knockout. In knockout cells, TNFα production was strongly downregulated upon the addition of H2O2, but NF‐κB in the basal condition and when TNFα was added was augmented, suggesting that these cells could respond to TNFα. These results indicated that BAP1 affects the expression of chemokines and cytokines, T and B cell migration, and activated inflammation associating with innate immunity.</description><identifier>ISSN: 1356-9597</identifier><identifier>EISSN: 1365-2443</identifier><identifier>DOI: 10.1111/gtc.12988</identifier><identifier>PMID: 36300836</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Actin ; Atrophy ; B cells ; BAP1 ; BRCA1 protein ; CC chemokine receptors ; CCL19 protein ; CCR7 protein ; CD69 antigen ; Cell adhesion & migration ; Cell lineage ; Cell migration ; chemokine and cytokine ; Chemokines ; CXCR5 protein ; Cytokines ; Histones ; Hydrogen peroxide ; Hydrolase ; Inflammation ; Innate immunity ; knockout ; Lymphocytes T ; Monocyte chemoattractant protein 1 ; Thymus ; TLR3 protein ; Toll-like receptors ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Tumor suppressor genes ; Ubiquitin</subject><ispartof>Genes to cells : devoted to molecular & cellular mechanisms, 2022-12, Vol.27 (12), p.731-740</ispartof><rights>2022 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4548-ed63dec0ea9c090a26a04fffac40644e388fab6488bd4f130a81b15e036950a33</citedby><cites>FETCH-LOGICAL-c4548-ed63dec0ea9c090a26a04fffac40644e388fab6488bd4f130a81b15e036950a33</cites><orcidid>0000-0001-5448-1215</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fgtc.12988$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fgtc.12988$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,1435,27933,27934,45583,45584,46418,46842</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36300836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takagi‐Kimura, Misato</creatorcontrib><creatorcontrib>Tada, Akio</creatorcontrib><creatorcontrib>Kijima, Takashi</creatorcontrib><creatorcontrib>Kubo, Shuji</creatorcontrib><creatorcontrib>Ohmuraya, Masaki</creatorcontrib><creatorcontrib>Yoshikawa, Yoshie</creatorcontrib><title>BAP1 depletion in human B‐lymphoblast cells affects the production of innate immune cytokines and chemokines</title><title>Genes to cells : devoted to molecular & cellular mechanisms</title><addtitle>Genes Cells</addtitle><description>BRCA1 associated protein 1 (BAP1) is a ubiquitin C‐terminal hydrolase that deubiquitinates histone H2AK119ub and other proteins and regulates the expression of multiple genes. The knockout of this tumor suppressor gene results in severe thymic atrophy, complete loss of the T cell lineage, and abnormal B cell development in mice. In the current study, we investigated in vitro effects of BAP1 knockout on cytokine and chemokine production using the human B‐lymphoblast cell line TSCE5. We confirmed that knockout changed the production of innate immune‐associated genes and their receptors. The CCL19, CCR7, CCL2, and CXCR5 genes associated with T and B cell migration were upregulated. Knockout cells producing high levels of CCL19 showed acceleration of actin polymerization, which is essential for cell migration. CD69, PTPRC, and TLR3 genes that activate inflammation were downregulated. The tumor necrosis factor ligand genes TNF, LTA, and TNFSF10 were downregulated by knockout. In knockout cells, TNFα production was strongly downregulated upon the addition of H2O2, but NF‐κB in the basal condition and when TNFα was added was augmented, suggesting that these cells could respond to TNFα. These results indicated that BAP1 affects the expression of chemokines and cytokines, T and B cell migration, and activated inflammation associating with innate immunity.</description><subject>Actin</subject><subject>Atrophy</subject><subject>B cells</subject><subject>BAP1</subject><subject>BRCA1 protein</subject><subject>CC chemokine receptors</subject><subject>CCL19 protein</subject><subject>CCR7 protein</subject><subject>CD69 antigen</subject><subject>Cell adhesion & migration</subject><subject>Cell lineage</subject><subject>Cell migration</subject><subject>chemokine and cytokine</subject><subject>Chemokines</subject><subject>CXCR5 protein</subject><subject>Cytokines</subject><subject>Histones</subject><subject>Hydrogen peroxide</subject><subject>Hydrolase</subject><subject>Inflammation</subject><subject>Innate immunity</subject><subject>knockout</subject><subject>Lymphocytes T</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Thymus</subject><subject>TLR3 protein</subject><subject>Toll-like receptors</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Tumor suppressor genes</subject><subject>Ubiquitin</subject><issn>1356-9597</issn><issn>1365-2443</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp1kc1KxDAUhYMo_i98AQm40UX1pvmZdKmDfyDoQtclTW-capuOTYvMzkfwGX0SM1ZdCGaTXPjO4dwcQvYYHLN4Th57e8zSTOsVssm4kkkqBF9dvqVKMplNNshWCE8AjKcg18kGVxxAc7VJ_NnpHaMlzmvsq9bTytPZ0BhPzz7e3utFM5-1RW1CTy3WdaDGObR9oP0M6bxry8F-qVoXhd70SKumGTxSu-jb58pjVPiS2hk247hD1pypA-5-39vk4eL8fnqV3NxeXk9PbxIrpNAJloqXaAFNZiEDkyoDwjlnrAAlBHKtnSmU0LoohWMcjGYFkwhcZRIM59vkcPSNIV8GDH3eVGG5gvHYDiFPJ2kmmdRiEtGDP-hTO3Q-pouU0ABSCRWpo5GyXRtChy6fd1VjukXOIF-WkMcS8q8SIrv_7TgUDZa_5M-vR-BkBF6rGhf_O-WX99PR8hNjnZIG</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Takagi‐Kimura, Misato</creator><creator>Tada, Akio</creator><creator>Kijima, Takashi</creator><creator>Kubo, Shuji</creator><creator>Ohmuraya, Masaki</creator><creator>Yoshikawa, Yoshie</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5448-1215</orcidid></search><sort><creationdate>202212</creationdate><title>BAP1 depletion in human B‐lymphoblast cells affects the production of innate immune cytokines and chemokines</title><author>Takagi‐Kimura, Misato ; Tada, Akio ; Kijima, Takashi ; Kubo, Shuji ; Ohmuraya, Masaki ; Yoshikawa, Yoshie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4548-ed63dec0ea9c090a26a04fffac40644e388fab6488bd4f130a81b15e036950a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Actin</topic><topic>Atrophy</topic><topic>B cells</topic><topic>BAP1</topic><topic>BRCA1 protein</topic><topic>CC chemokine receptors</topic><topic>CCL19 protein</topic><topic>CCR7 protein</topic><topic>CD69 antigen</topic><topic>Cell adhesion & migration</topic><topic>Cell lineage</topic><topic>Cell migration</topic><topic>chemokine and cytokine</topic><topic>Chemokines</topic><topic>CXCR5 protein</topic><topic>Cytokines</topic><topic>Histones</topic><topic>Hydrogen peroxide</topic><topic>Hydrolase</topic><topic>Inflammation</topic><topic>Innate immunity</topic><topic>knockout</topic><topic>Lymphocytes T</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Thymus</topic><topic>TLR3 protein</topic><topic>Toll-like receptors</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><topic>Tumor suppressor genes</topic><topic>Ubiquitin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takagi‐Kimura, Misato</creatorcontrib><creatorcontrib>Tada, Akio</creatorcontrib><creatorcontrib>Kijima, Takashi</creatorcontrib><creatorcontrib>Kubo, Shuji</creatorcontrib><creatorcontrib>Ohmuraya, Masaki</creatorcontrib><creatorcontrib>Yoshikawa, Yoshie</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Genes to cells : devoted to molecular & cellular mechanisms</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takagi‐Kimura, Misato</au><au>Tada, Akio</au><au>Kijima, Takashi</au><au>Kubo, Shuji</au><au>Ohmuraya, Masaki</au><au>Yoshikawa, Yoshie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BAP1 depletion in human B‐lymphoblast cells affects the production of innate immune cytokines and chemokines</atitle><jtitle>Genes to cells : devoted to molecular & cellular mechanisms</jtitle><addtitle>Genes Cells</addtitle><date>2022-12</date><risdate>2022</risdate><volume>27</volume><issue>12</issue><spage>731</spage><epage>740</epage><pages>731-740</pages><issn>1356-9597</issn><eissn>1365-2443</eissn><abstract>BRCA1 associated protein 1 (BAP1) is a ubiquitin C‐terminal hydrolase that deubiquitinates histone H2AK119ub and other proteins and regulates the expression of multiple genes. The knockout of this tumor suppressor gene results in severe thymic atrophy, complete loss of the T cell lineage, and abnormal B cell development in mice. In the current study, we investigated in vitro effects of BAP1 knockout on cytokine and chemokine production using the human B‐lymphoblast cell line TSCE5. We confirmed that knockout changed the production of innate immune‐associated genes and their receptors. The CCL19, CCR7, CCL2, and CXCR5 genes associated with T and B cell migration were upregulated. Knockout cells producing high levels of CCL19 showed acceleration of actin polymerization, which is essential for cell migration. CD69, PTPRC, and TLR3 genes that activate inflammation were downregulated. The tumor necrosis factor ligand genes TNF, LTA, and TNFSF10 were downregulated by knockout. In knockout cells, TNFα production was strongly downregulated upon the addition of H2O2, but NF‐κB in the basal condition and when TNFα was added was augmented, suggesting that these cells could respond to TNFα. These results indicated that BAP1 affects the expression of chemokines and cytokines, T and B cell migration, and activated inflammation associating with innate immunity.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36300836</pmid><doi>10.1111/gtc.12988</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-5448-1215</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Actin Atrophy B cells BAP1 BRCA1 protein CC chemokine receptors CCL19 protein CCR7 protein CD69 antigen Cell adhesion & migration Cell lineage Cell migration chemokine and cytokine Chemokines CXCR5 protein Cytokines Histones Hydrogen peroxide Hydrolase Inflammation Innate immunity knockout Lymphocytes T Monocyte chemoattractant protein 1 Thymus TLR3 protein Toll-like receptors Tumor necrosis factor-TNF Tumor necrosis factor-α Tumor suppressor genes Ubiquitin |
| title | BAP1 depletion in human B‐lymphoblast cells affects the production of innate immune cytokines and chemokines |
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