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Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer
- Source :
- Proceedings of the National Academy of Sciences. 110:9862-9867
- Publication Year :
- 2013
- Publisher :
- Proceedings of the National Academy of Sciences, 2013.
-
Abstract
- 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.
- Subjects :
- Male
Chemokine
Inflammasomes
Receptors, Cell Surface
Inflammation
medicine.disease_cause
Pyrin domain
Epithelium
CCL5
Pathogenesis
Mice
Neoplasms
medicine
Animals
Chemokine CCL5
Mice, Knockout
NLRP6
Multidisciplinary
biology
Interleukin-6
Interleukin-18
Inflammasome
Colonoscopy
Biological Sciences
Colitis
digestive system diseases
Mice, Inbred C57BL
Immunology
biology.protein
Cancer research
Metagenome
Female
medicine.symptom
Colorectal Neoplasms
Carcinogenesis
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 110
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....a52124ac65470e703b4e8a4ad190a272