Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production

• Willscott E. Naugler

  Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.

• Toshiharu Sakurai

  Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.

• Sunhwa Kim

  Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.

• Shin Maeda

  Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.

• KyoungHyun Kim

  Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.

• Ahmed M. Elsharkawy

  Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.

• Michael Karin

  Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.

抄録

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.

収録刊行物

• Science

  Science 317 (5834), 121-124, 2007-07-06

  American Association for the Advancement of Science (AAAS)

キーワード

• Multidisciplinary

詳細情報

• CRID: 1361699995808094720
• NII論文ID: 80018290293
• DOI: 10.1126/science.1140485
• ISSN: 10959203
• ISSN: 00368075
• Web Site: https://www.science.org/doi/pdf/10.1126/science.1140485
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