Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production Export

@article{citeulike:1447407, 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. 10.1126/science.1140485}, author = {Naugler, Willscott E. and Sakurai, Toshiharu and Kim, Sunhwa and Maeda, Shin and Kim, Kyounghyun and Elsharkawy, Ahmed M. and Karin, Michael}, citeulike-article-id = {1447407}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1140485}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/317/5834/121}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17615358}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17615358}, day = {6}, doi = {10.1126/science.1140485}, journal = {Science}, keywords = {cancer, inflammation}, month = {July}, number = {5834}, pages = {121--124}, posted-at = {2007-07-14 15:36:42}, priority = {2}, title = {Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production}, url = {http://dx.doi.org/10.1126/science.1140485}, volume = {317}, year = {2007} }

TY - JOUR ID - citeulike:1447407 L3 - citeulike-article-id:1447407 N2 - 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. 10.1126/science.1140485 IS - 5834 JF - Science EP - 124 TI - Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production VL - 317 SP - 121 KW - cancer KW - inflammation AU - Naugler, Willscott AU - Sakurai, Toshiharu AU - Kim, Sunhwa AU - Maeda, Shin AU - Kim, Kyounghyun AU - Elsharkawy, Ahmed AU - Karin, Michael PY - 2007/07/06/ UR - http://dx.doi.org/10.1126/science.1140485 ER -