{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:08:27Z","timestamp":1780081707619,"version":"3.54.0"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T00:00:00Z","timestamp":1668902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T00:00:00Z","timestamp":1668902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172128"],"award-info":[{"award-number":["82172128"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012491","name":"Beijing Municipal Excellent Talents Foundation","doi-asserted-by":"publisher","award":["2018000021223ZK27"],"award-info":[{"award-number":["2018000021223ZK27"]}],"id":[{"id":"10.13039\/100012491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflamm. Res."],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>Cytokine storm syndrome is a fatal condition related to infectious and autoimmune diseases. Here, we aim to investigate the regulatory mechanisms of Blimp-1 on multiple cytokine production.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The <jats:italic>Blimp1<\/jats:italic> shRNA was transfected into RAW264.7 macrophages, followed by Toll-like receptor (TLR) ligand stimulation. The mRNA and protein levels of cytokines were detected by real-time PCR and flow cytometric bead array. The nuclear translocation of AP-1 and NF-\u03baB p65 was measured by immunofluorescence staining. The transcriptional activity was detected by luciferase reporter assay with 5\u2009\u00d7\u2009NF-\u03baB reporter or with IL6 promoter reporter.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Blimp-1 significantly inhibited the expression and secretion of IL-1\u03b2, IL-6, and IL-18 in macrophages during stimulation with a variety of TLR ligands. The immunofluorescence staining results showed that Blimp-1 strictly controlled the nuclear translocation of NF-\u03baB p65 in LPS-challenged macrophages. Furthermore, Blimp-1 directly inhibited the transcriptional activity of NF-\u03baB and the transcription of IL6 gene.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Blimp-1 represses the production of multiple pro-inflammatory cytokines by directly binding the genomic region and restricting the nuclear translocation and transcriptional activity of NF-\u03baB. This finding may provide potential therapeutic strategies for the cytokine storm-related diseases.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00011-022-01671-2","type":"journal-article","created":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T14:02:25Z","timestamp":1668952945000},"page":"217-220","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multi-target regulation of pro-inflammatory cytokine production by transcription factor Blimp-1"],"prefix":"10.1007","volume":"72","author":[{"given":"Qiushi","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwei","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuluan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,20]]},"reference":[{"key":"1671_CR1","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1056\/NEJMra2026131","volume":"383","author":"DC Fajgenbaum","year":"2020","unstructured":"Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020;383:2255\u201373.","journal-title":"N Engl J Med"},{"key":"1671_CR2","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/S0140-6736(08)60453-5","volume":"371","author":"JS Smolen","year":"2008","unstructured":"Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371:987\u201397.","journal-title":"Lancet"},{"key":"1671_CR3","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.immuni.2019.12.007","volume":"52","author":"A Sledzinska","year":"2020","unstructured":"Sledzinska A, Vila de Mucha M, Bergerhoff K, Hotblack A, Demane DF, Ghorani E, et al. Regulatory T cells restrain interleukin-2- and blimp-1-dependent acquisition of cytotoxic function by CD4(+) T cells. Immunity. 2020;52:151-166 e6.","journal-title":"Immunity"},{"key":"1671_CR4","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/ni.1837","volume":"11","author":"S Crotty","year":"2010","unstructured":"Crotty S, Johnston RJ, Schoenberger SP. Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation. Nat Immunol. 2010;11:114\u201320.","journal-title":"Nat Immunol"},{"key":"1671_CR5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.805260","volume":"12","author":"S Nadeau","year":"2021","unstructured":"Nadeau S, Martins GA. Conserved and unique functions of blimp1 in immune cells. Front Immunol. 2021;12: 805260.","journal-title":"Front Immunol"},{"key":"1671_CR6","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1111\/imm.13249","volume":"161","author":"I Ulmert","year":"2020","unstructured":"Ulmert I, Henriques-Oliveira L, Pereira CF, Lahl K. Mononuclear phagocyte regulation by the transcription factor Blimp-1 in health and disease. Immunology. 2020;161:303\u201313.","journal-title":"Immunology"},{"key":"1671_CR7","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1084\/jem.20110658","volume":"208","author":"SJ Kim","year":"2011","unstructured":"Kim SJ, Zou YR, Goldstein J, Reizis B, Diamond B. Tolerogenic function of Blimp-1 in dendritic cells. J Exp Med. 2011;208:2193\u20139.","journal-title":"J Exp Med"},{"key":"1671_CR8","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s13045-017-0486-z","volume":"10","author":"L Zhu","year":"2017","unstructured":"Zhu L, Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, et al. Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia. J Hematol Oncol. 2017;10:124.","journal-title":"J Hematol Oncol"},{"key":"1671_CR9","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.immuni.2013.08.032","volume":"39","author":"HM Shin","year":"2013","unstructured":"Shin HM, Kapoor V, Guan T, Kaech SM, Welsh RM, Berg LJ. Epigenetic modifications induced by Blimp-1 regulate CD8(+) T cell memory progression during acute virus infection. Immunity. 2013;39:661\u201375.","journal-title":"Immunity"},{"key":"1671_CR10","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1021\/acsinfecdis.9b00186","volume":"5","author":"G Saha","year":"2019","unstructured":"Saha G, Khamar BM, Prerna K, Kumar M, Dubey VK. BLIMP-1 plays important role in the regulation of macrophage pyroptosis for the growth and multiplication of Leishmania donovani. ACS Infect Dis. 2019;5:2087\u201395.","journal-title":"ACS Infect Dis"},{"key":"1671_CR11","doi-asserted-by":"publisher","first-page":"2592","DOI":"10.1128\/MCB.20.7.2592-2603.2000","volume":"20","author":"J Yu","year":"2000","unstructured":"Yu J, Angelin-Duclos C, Greenwood J, Liao J, Calame K. Transcriptional repression by blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase. Mol Cell Biol. 2000;20:2592\u2013603.","journal-title":"Mol Cell Biol"}],"container-title":["Inflammation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-022-01671-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00011-022-01671-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-022-01671-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T03:06:49Z","timestamp":1676344009000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00011-022-01671-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,20]]},"references-count":11,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["1671"],"URL":"https:\/\/doi.org\/10.1007\/s00011-022-01671-2","relation":{},"ISSN":["1023-3830","1420-908X"],"issn-type":[{"value":"1023-3830","type":"print"},{"value":"1420-908X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,20]]},"assertion":[{"value":"18 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}