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Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production

Lookup NU author(s): Dr Ahmed Elsharkawy, Professor Muhammad Karim

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Abstract

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.

Publication metadata

Author(s): Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M

Publication type: Article

Publication status: Published

Journal: Science

Year: 2007

Volume: 317

Issue: 5834

Pages: 121-124

ISSN (print): 0036-8075

ISSN (electronic): 1095-9203

Publisher: American Association for the Advancement of Science

URL: http://dx.doi.org/10.1126/science.1140485

DOI: 10.1126/science.1140485

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