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Lookup NU author(s): Dr Ahmed Elsharkawy,
Professor Muhammad Karim
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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.
Author(s): Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M
Publication type: Article
Publication status: Published
ISSN (print): 0036-8075
ISSN (electronic): 1095-9203
Publisher: American Association for the Advancement of Science
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