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  • 标题:Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer
  • 本地全文:下载
  • 作者:Bo Hu ; Eran Elinav ; Samuel Huber
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2013
  • 卷号:110
  • 期号:24
  • 页码:9862-9867
  • DOI:10.1073/pnas.1307575110
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The microbiota is pivotal in the pathogenesis of inflammatory bowel disease (IBD)-associated inflammation-induced colorectal cancer (CRC), yet mechanisms for these effects remain poorly characterized. Here, we demonstrate that aberrant inflammasome-induced microbiota plays a critical role in CRC development, where mice deficient in the NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome feature enhanced inflammation-induced CRC formation. Intriguingly, WT mice cohoused either with inflammasome-deficient mice or with mice lacking IL-18 feature exacerbated inflammation-induced CRC compared with singly housed WT mice. Enhanced tumorigenesis is dependent on microbiota-induced chemokine (C-C motif) ligand 5 (CCL5)-driven inflammation, which in turn promotes epithelial cell proliferation through local activation of the IL-6 pathway, leading to cancer formation. Altogether, our results mechanistically link the altered microbiota with the pathogenesis of inflammation-induced CRC and suggest that in some conditions, microbiota components may transfer CRC susceptibility between individuals.
  • 关键词:colon cancer ; microflora ; ASC
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