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Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
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Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
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Journal Article
Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
2007
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ Biological and medical sciences
/ Cancer
/ Carbon Tetrachloride - administration & dosage
/ Corn oil
/ Diethylnitrosamine - administration & dosage
/ Diethylnitrosamine - metabolism
/ Female
/ Females
/ Gastroenterology. Liver. Pancreas. Abdomen
/ hepatoma
/ Liver
/ Liver Neoplasms, Experimental - chemically induced
/ Liver Neoplasms, Experimental - immunology
/ Liver Neoplasms, Experimental - physiopathology
/ Liver. Biliary tract. Portal circulation. Exocrine pancreas
/ Male
/ Males
/ men
/ Mice
/ Myeloid Differentiation Factor 88 - physiology
/ Necrosis
/ Oncology
/ risk
/ Tumors
