Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
Open accessAbstract
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.
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IL-6 appears to be an essential factor common to the induction of HCC by a variety of stimuli, including chemical, obesity and FGF19.
“Notably, IL-6 appears to be an essential factor common to the induction of HCC by a variety of stimuli, including chemical61, obesity62 and FGF19.”
From Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis (2017) · cites this paper as [61]
Eritoran and resatorvid improved survival in animal sepsis models but did not reduce mortality in patients with severe sepsis.
“Eritoran130 and resatorvid131 improved survival in animal models of sepsis, but did not reduce mortality in patients with severe sepsis132,133.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [131]
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- Authors
- Naugler, W. E., Sakurai, T., Kim, S., Maeda, S., Kim, K., Elsharkawy, A. M., & Karin, M.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Karin, Michael
- ORCID
- Venue
- Science
- Published
- 2007-07-06
- Volume
- 317
- Issue
- 5834
- Pages
- 121-124
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2039845199
- Cited by
- 1,955
- References
- 28
- Citations by year
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- FWCI
- 74.17
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Cancer Institute (R01CA118165, CA118165, T32CA121938)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK007202, T32DK007202)
- National Institute of Environmental Health Sciences (ES004151, ES-006376, R01ES006376)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- hepatocellular carcinoma, sex differences, liver cancer, MyD88, interleukin-6, Kupffer cells, diethylnitrosamine, hepatocarcinogenesis, estrogen, Toll-like receptor signaling, cancer prevention
- MeSH terms
- Animals, Carbon Tetrachloride, Diethylnitrosamine, Estradiol, Female, Kupffer Cells, Liver, Liver Neoplasms, Experimental, Male, Mice, Inbred C57BL, Necrosis, Ovariectomy, RNA, Messenger, Sex Characteristics, Interleukin-6, Mice, Knockout, Hepatocytes, Mice, Myeloid Differentiation Factor 88
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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