SR-A1 suppresses colon inflammation and tumorigenesis through negative regulation of NF-kappa B signaling
SR-A1 suppresses colon inflammation and tumorigenesis through negative regulation of NF-kappa B signaling
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SR-A1 通过负调节 NF-κ B 信号传导抑制结肠炎症和肿瘤发生
DOI：
10.1016/j.bcp.2018.05.017
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发表时间：
2018
影响因子：
5.8
通讯作者：
Chen Qi
中科院分区：
文献类型：
--
作者：
Zong Guijuan;Zhu Yaqin;Zhang Yan;Wang Yan;Bai Hui;Yang Qing;Zhang Hanwen;Li Xiaoyu;Zhu Xudong;Chen Qi
炎症性肠病的特征在于与发生结直肠癌的风险增加相关的慢性肠道炎症性疾病。然而，详细的机制并不完全清楚。本研究的目的是确定巨噬细胞清道夫受体A1类（SR-A1），主要在巨噬细胞中表达的模式识别受体，对结肠炎的影响，并阐明其潜在的机制。我们发现SR-A1−/−小鼠加重了葡聚糖硫酸钠诱导的急性和复发性结肠炎。这一作用与结肠中经典和非经典NF-κB信号的强烈激活有关。SR-A1对非经典NF-κB信号的抑制作用可能是通过与TRAF 3相互作用实现的。此外，SR-A1的抗炎作用可以抑制小鼠结肠炎相关癌症的发生。这些结果首次证明了SR-A1作为炎症性肠病的抑制剂。
Inflammatory bowel disease is characterized by chronic intestinal inflammatory disorders associated with increased risk of developing colorectal cancer. However, the detailed mechanisms are not fully understood. The aim of this study was to determine the effect of macrophage scavenger receptor class A1 (SR-A1), a pattern recognition receptor primarily expressed in macrophages, on colitis and clarify the underlying mechanisms. We found that SR-A1−/−mice had an aggravating dextran sodium sulfate-induced acute and recurring colitis. This action was associated with a robust activation of both canonical and noncanonical NF-κB signaling in the colon. Suppression of the noncanonical NF-κB signaling by SR-A1 may be via its interaction with TRAF3 in macrophages. Furthermore, the anti-inflammation effect of SR-A1 could inhibit occurrence of colitis-associated cancer in mice. These results, for the first time, demonstrate that SR-A1 as a suppressor for inflammatory bowel disease.