title: Protective function of interleukin 27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells.
abstract: 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-27Rα (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-α, GM-CSF and CXCL1 triggeredin vitroby 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.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Bijun
authors.initials: B
authors.lastname: Cui
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Lu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Lai
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Pan
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Luoquan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China; National Key Laboratory of Medical Molecular Biology and Department of Immunology, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine , Hangzhou, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
keywords: CXCL1; Colitis-associated cancer; inflammation; interleukin 27; intestinal epithelial cells