期刊
ONCOIMMUNOLOGY
卷 6, 期 2, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2016.1268309
关键词
Colitis-associated cancer; CXCL1; inflammation; interleukin 27; intestinal epithelial cells
资金
- National Program on Key Basic Research Project [2014CB542101, 2013CB530502]
- National Natural Science Foundation of China [81230074, 81373115]
- Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents
- Zhejiang Provincial Program for Innovative Research Team in Zhejiang Province [2010R50046]
Numerous studies have demonstrated that inflammation contributes to a variety of cancer formation, among them, colitis-associated cancer (CAC) represents a typical inflammation-related cancer. Interleukin 27 (IL-27) has been demonstrated to play an important role in inflammation-related disease. The effect of IL-27 in intestinal inflammation is controversial and its role in CAC is not elucidated yet. In our present study, we found that IL-27 has protective function in murine model of CAC through suppression of inflammatory cytokines in intestinal epithelial cells (IECs). IL-27R alpha (WSX-1) deficiency promotes the CAC development in mice, which is driven by enhanced tumor cell proliferation, more intensive myeloid-derived suppressor cells (MDSC) accumulation in colon lamina propria and higher level of inflammatory cytokines and chemokines in IECs. The levels of IL-6, TNF-alpha, GM-CSF and CXCL1 triggered in vitro by toll-like receptor ligands are significantly upregulated in IECs from WSX-1 KO mice. Removal of commensal microorganism through antibiotic treatment in mice to eliminate TLR ligands deprives the protective function of IL-27 on CAC tumor growth. Thus, IL-27 suppresses CAC formation through an anti-inflammation mechanism targeting IECs and in turn resists the tumorigenesis. Hence, our study explained how IL-27 exerts its anti-inflammatory function on epithelial cells to fight against chronic-inflammation-associated cancer, which might provide new insights on the potential therapeutic strategies for cancer.
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