Sun Chongjun, Shen Haokun, Cai Haiming, Zhao Zengjue, Gan Guanhua, Feng Saixiang, Chu Pinpin, Zeng Min, Deng Jinbo, Ming Feiping, Ma Miaopeng, Jia Junhao, He Rongxiao, Cao Ding, Chen Zhiyang, Li Jiayi, Zhang Linghua
Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China.
Biochem Pharmacol. 2021 Jun;188:114586. doi: 10.1016/j.bcp.2021.114586. Epub 2021 Apr 29.
Mycotoxin contamination is an ongoing and growing issue that can create health risks and even cause death. Unfortunately, there is currently a lack of specific therapy against mycotoxins with few side effects. On the other hand, the strategic expression of CXCL17 in mucosal tissues suggests that it may be involved in immune response when exposed to mycotoxins, but the exact role of CXCL17 remains largely unknown. Using Caco-2 as a cell model of the intestinal epithelial barrier (the first line of defense against mycotoxins), we showed that a strong production of ROS-dependent CXCL17 was triggered by mycotoxins via p38 and JNK pathways. Under the mycotoxins stress, CXCL17 modulated enhanced immuno-protective response with a remission of inflammation and apoptosis through PI3K/AKT/mTOR. Based on our observed feedback of CXCL17 to the mycotoxins, we developed the CXCL17-mimetic peptides in silico (CX1 and CX2) that possessed the safety and the capability to ameliorate mycotoxins-inducible inflammation and apoptosis. In this study, the identification of detoxifying feature of CXCL17 is a prominent addition to the chemokine field, pointing out a new direction for curing the mycotoxins-caused damage.
霉菌毒素污染是一个持续且日益严重的问题，会带来健康风险甚至导致死亡。不幸的是，目前缺乏针对霉菌毒素且副作用小的特效疗法。另一方面，CXCL17在黏膜组织中的策略性表达表明，它在接触霉菌毒素时可能参与免疫反应，但CXCL17的确切作用在很大程度上仍不清楚。我们以Caco-2作为肠道上皮屏障（抵御霉菌毒素的第一道防线）的细胞模型，发现霉菌毒素通过p38和JNK途径触发了依赖ROS的CXCL17的强烈产生。在霉菌毒素应激下，CXCL17通过PI3K/AKT/mTOR调节增强免疫保护反应，减轻炎症和细胞凋亡。基于我们观察到的CXCL17对霉菌毒素的反馈，我们在计算机上设计了具有安全性且能够改善霉菌毒素诱导的炎症和细胞凋亡的CXCL17模拟肽（CX1和CX2）。在本研究中，CXCL17解毒特性的鉴定是趋化因子领域的一项突出成果，为治疗霉菌毒素造成的损伤指明了新方向。
