Prieto Jesús
Liver Unit and Division of Hepatology and Gene Therapy, University Clinic and Center for Applied Medical Research, CIBERehd University of Navarra, Pamplona, Spain.
J Hepatol. 2008 Feb;48(2):380-1. doi: 10.1016/j.jhep.2007.11.007. Epub 2007 Dec 5.
Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M. 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. [Abstract reproduced by permission of Science 2007;317:121-124].
由于MyD88依赖的白细胞介素-6产生存在性别差异，导致肝癌的性别差异。瑙格勒·W·E、樱井·T、金·S、前田·S、金·K、埃尔沙尔卡维·A·M、卡林·M。肝细胞癌（HCC）是最常见的肝癌，主要发生在男性身上。在给予化学致癌物二乙基亚硝胺（DEN）的小鼠中也观察到类似的性别差异。给予DEN后，雄性小鼠血清白细胞介素-6（IL-6）浓度的升高幅度大于雌性小鼠。此外，IL-6的缺失消除了小鼠肝癌发生中的性别差异。DEN暴露以依赖Toll样受体衔接蛋白MyD88的方式促进库普弗细胞（KC）中IL-6的产生，MyD88的缺失也保护雄性小鼠免受DEN诱导的肝癌发生。雌激素抑制暴露于坏死肝细胞的KC分泌IL-6，并降低DEN处理的雄性小鼠循环中IL-6的浓度。我们提出，雌激素介导的KC对IL-6产生的抑制降低了女性患肝癌的风险，这些发现可能用于预防男性的HCC。[摘要经《科学》2007年；317:121 - 124许可转载]
