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Science 6 July 2007: Vol. 317. no. 5834, pp. 121 - 124 DOI: 10.1126/science.1140485
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Reports
Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
Willscott E. Naugler,1,2
Toshiharu Sakurai,1
Sunhwa Kim,1
Shin Maeda,3
KyoungHyun Kim,1
Ahmed M. Elsharkawy,1,4
Michael Karin1*
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.
1 Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.
2 Department of Medicine, Division of Gastroenterology, University of California, San Diego, CA 93093, USA.
3 Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan.
4 Liver Research Group, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK.
* To whom correspondence should be addressed: 9500 Gilman Road, Mail Code 0723 University of California, San Diego, San Diego, CA 920930636, USA. E-mail: karinoffice{at}ucsd.edu
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- S. Seshadri, Y. Kannan, S. Mitra, J. Parker-Barnes, and M. D. Wewers (2009)
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- A. Hendifar, D. Yang, F. Lenz, G. Lurje, A. Pohl, C. Lenz, Y. Ning, W. Zhang, and H.-J. Lenz (2009)
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| PDF »
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| Full Text »
| PDF »
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| Full Text »
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| Full Text »
| PDF »
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283, 25900-25912
| Abstract »
| Full Text »
| PDF »
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- J. M. Phillips and J. I. Goodman (2008)
Toxicol. Sci.
104, 86-99
| Abstract »
| Full Text »
| PDF »
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- M. Dougan and G. Dranoff (2008)
J. Exp. Med.
205, 267-270
| Abstract »
| Full Text »
| PDF »
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| Abstract »
| Full Text »
| PDF »
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- M. C. Siracusa, M. G. Overstreet, F. Housseau, A. L. Scott, and S. L. Klein (2008)
J. Immunol.
180, 1423-1431
| Abstract »
| Full Text »
| PDF »
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- K. J. Riehle, J. S. Campbell, R. S. McMahan, M. M. Johnson, R. P. Beyer, T. K. Bammler, and N. Fausto (2008)
J. Exp. Med.
205, 91-103
| Abstract »
| Full Text »
| PDF »
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- J. B. Swann, M. D. Vesely, A. Silva, J. Sharkey, S. Akira, R. D. Schreiber, and M. J. Smyth (2008)
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105, 652-656
| Abstract »
| Full Text »
| PDF »
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- S. Ikuta, H. Edamatsu, M. Li, L. Hu, and T. Kataoka (2008)
Cancer Res.
68, 64-72
| Abstract »
| Full Text »
| PDF »
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- A. B. Rogers, E. J. Theve, Y. Feng, R. C. Fry, K. Taghizadeh, K. M. Clapp, C. Boussahmain, K. S. Cormier, and J. G. Fox (2007)
Cancer Res.
67, 11536-11546
| Abstract »
| Full Text »
| PDF »
- Hepatocellular Carcinoma and Sex.
- J. Wands (2007)
N. Engl. J. Med.
357, 1974-1976
| Full Text »
| PDF »
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