{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:54:50Z","timestamp":1792979690150,"version":"4.5.0"},"reference-count":30,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5834","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2007,7,6]]},"abstract":"<jats:p>Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.<\/jats:p>","DOI":"10.1126\/science.1140485","type":"journal-article","created":{"date-parts":[[2007,7,5]],"date-time":"2007-07-05T22:02:41Z","timestamp":1183672961000},"page":"121-124","source":"Crossref","is-referenced-by-count":1689,"title":["Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production"],"prefix":"10.1126","volume":"317","author":[{"given":"Willscott E.","family":"Naugler","sequence":"first","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA."},{"name":"Department of Medicine, Division of Gastroenterology, University of California, San Diego, CA 93093, USA."},{"name":"Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan."},{"name":"Liver Research Group, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiharu","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA."},{"name":"Department of Medicine, Division of Gastroenterology, University of California, San Diego, CA 93093, USA."},{"name":"Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan."},{"name":"Liver Research Group, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhwa","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA."},{"name":"Department of Medicine, Division of Gastroenterology, University of California, San Diego, CA 93093, USA."},{"name":"Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan."},{"name":"Liver Research Group, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Maeda","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA."},{"name":"Department of Medicine, Division of Gastroenterology, University of California, San Diego, CA 93093, USA."},{"name":"Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan."},{"name":"Liver Research Group, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KyoungHyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA."},{"name":"Department of Medicine, Division of Gastroenterology, University of California, San Diego, CA 93093, USA."},{"name":"Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan."},{"name":"Liver Research Group, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Elsharkawy","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA."},{"name":"Department of Medicine, Division of Gastroenterology, University of California, San Diego, CA 93093, USA."},{"name":"Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan."},{"name":"Liver Research Group, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Karin","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA."},{"name":"Department of Medicine, Division of Gastroenterology, University of California, San Diego, CA 93093, USA."},{"name":"Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan."},{"name":"Liver Research 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DEN administration to TRIF \u2013\/\u2013 mice resulted in as much IL-6 induction as seen in WT mice."},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.016"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1594"},{"key":"e_1_3_1_31_2","unstructured":"We thank J. Feramisco for help with image capture and analysis and E. Karin for help with the surgical models. Supported by National Institute of Diabetes and Digestive and Kidney Diseases grant DK007202 (W.E.N.); Japan Society for the Promotion of Science (T.S.); Human Frontier Science Program (S.K.); and NIH grants ES004151 and ES006376 CA118165 and the Superfund Basic Research Program (M.K.). M.K. is an American Cancer Society Professor."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1140485","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T05:02:00Z","timestamp":1704862920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1140485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,7,6]]},"references-count":30,"journal-issue":{"issue":"5834","published-print":{"date-parts":[[2007,7,6]]}},"alternative-id":["10.1126\/science.1140485"],"URL":"https:\/\/doi.org\/10.1126\/science.1140485","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1088587.542668","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,7,6]]}}}