Protective function of interleukin 27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells
Protective function of interleukin 27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells
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白细胞介素 27 通过抑制肠上皮细胞中的炎症细胞因子对结肠炎相关癌症发挥保护作用
DOI：
10.1080/2162402x.2016.1268309
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发表时间：
2017-01-01
期刊：
影响因子：
7.2
通讯作者：
Wang, Qingqing
中科院分区：
文献类型：
--
作者：
Cui, Bijun;Lu, Shen;Wang, Qingqing
大量研究表明，炎症与多种癌症的形成有关，其中结肠炎相关癌(CAC)是一种典型的炎症相关性癌症。白介素27(IL-27)已被证明在炎症相关疾病中发挥重要作用。IL-27在肠道炎症中的作用存在争议，其在CAC中的作用尚不清楚。在本研究中，我们发现IL-27通过抑制肠上皮细胞(IECS)中的炎性细胞因子对CAC模型小鼠具有保护作用。IL-27Rα(WSX-1)缺乏促进了小鼠CAC的发生发展，其机制可能与肿瘤细胞增殖增强、结肠固有层髓系抑制细胞(MDSC)大量聚集以及IECs中炎性细胞因子和趋化因子水平升高有关。Toll样受体配体在体外可显著上调WSX-1KO小鼠IECs中IL-6、TNF-α、GM-CSF和CXCL1的水平。通过抗生素治疗清除小鼠的共生微生物以消除TLR配体，剥夺了IL-27对CAC肿瘤生长的保护功能。因此，IL-27通过针对IECs的抗炎机制抑制CAC的形成，进而抑制肿瘤的发生。因此，我们的研究解释了IL-27如何在上皮细胞上发挥抗炎作用来对抗慢性炎症相关的癌症，这可能为癌症的潜在治疗策略提供新的见解。
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.