{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T09:10:00Z","timestamp":1792401000521,"version":"4.4.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,2,9]]},"abstract":"<jats:p>IL-1\u03b1, like IL-1\u03b2, possesses multiple inflammatory and immune properties. However, unlike IL-1\u03b2, the cytokine is present intracellularly in healthy tissues and is not actively secreted. Rather, IL-1\u03b1 translocates to the nucleus and participates in transcription. Here we show that intracellular IL-1\u03b1 is a chromatin-associated cytokine and highly dynamic in the nucleus of living cells. During apoptosis, IL-1\u03b1 concentrates in dense nuclear foci, which markedly reduces its mobile nature. In apoptotic cells, IL-1\u03b1 is retained within the chromatin fraction and is not released along with the cytoplasmic contents. To simulate the in vivo inflammatory response to cells undergoing different mechanisms of death, lysates of cells were embedded in Matrigel plugs and implanted into mice. Lysates from cells undergoing necrosis recruited cells of the myeloid lineage into the Matrigel, whereas lysates of necrotic cells lacking IL-1\u03b1 failed to recruit an infiltrate. In contrast, lysates of cells undergoing apoptotic death were inactive. Cells infiltrating the Matrigel were due to low concentrations (20\u201350 pg) of the IL-1\u03b1 precursor containing the receptor interacting C-terminal, whereas the N-terminal propiece containing the nuclear localization site failed to do so. When normal keratinocytes were subjected to hypoxia, the constitutive IL-1\u03b1 precursor was released into the supernatant. Thus, after an ischemic event, the IL-1\u03b1 precursor is released by hypoxic cells and incites an inflammatory response by recruiting myeloid cells into the area. Tissues surrounding the necrotic site also sustain damage from the myeloid cells. Nuclear trafficking and differential release during necrosis vs. apoptosis demonstrate that inflammation by IL-1\u03b1 is tightly controlled.<\/jats:p>","DOI":"10.1073\/pnas.0915018107","type":"journal-article","created":{"date-parts":[[2010,1,25]],"date-time":"2010-01-25T21:54:47Z","timestamp":1264456487000},"page":"2574-2579","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":311,"title":["Differential release of chromatin-bound IL-1\u03b1 discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation"],"prefix":"10.1073","volume":"107","author":[{"given":"Idan","family":"Cohen","sequence":"first","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology and Faculty of Health Sciences and Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peleg","family":"Rider","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology and Faculty of Health Sciences and Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaron","family":"Carmi","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology and Faculty of Health Sciences and Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Braiman","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology and Faculty of Health Sciences and Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahar","family":"Dotan","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology and Faculty of Health Sciences and Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malka R.","family":"White","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology and Faculty of Health Sciences and Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Voronov","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology and Faculty of Health Sciences and Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael U.","family":"Martin","sequence":"additional","affiliation":[{"name":"Immunology FB08, Justus-Liebig-University Giessen, D-35394 Giessen, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Dinarello","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver, Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron N.","family":"Apte","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology and Faculty of Health Sciences and Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,1,25]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00615.x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)61450-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306342200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308705101"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00858"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1104648"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2004.04.007"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1189\/jlb.72.6.1084","article-title":"HMGB1 as a DNA-binding cytokine","volume":"72","author":"Andersson U","year":"2002","unstructured":"U Andersson, H Erlandsson-Harris, H Yang, KJ Tracey, HMGB1 as a DNA-binding cytokine. 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