Protective Function of Novel Fungal Immunomodulatory Proteins Fip-lti1 and Fip-lti2 from Lentinus tigrinus in Concanavalin A-Induced Liver Oxidative Injury

文献类型： 外文期刊

第一作者： Gao, Yingnyu

作者： Gao, Yingnyu;Wang, Ying;Wang, Ying;Wu, Yingying;Chen, Hongyu;Yang, Ruiheng;Bao, Dapeng;Gao, Yingnyu

作者机构：

期刊名称：OXIDATIVE MEDICINE AND CELLULAR LONGEVITY （ 影响因子：6.543； 五年影响因子：7.454 ）

ISSN： 1942-0900

年卷期： 2019 年

页码：

收录情况： SCI

摘要： Fungal immunomodulatory proteins (FIPs) are a class of small proteins that have been extensively studied for their immunomodulatory activities. In this study, two novel FIPs from Lentinus tigrinus were identified and named Fip-lti1 and Fip-lti2. The bioactive characteristics of Fip-lti1 and Fip-lti2 were compared to a well-known FIP (12-8 from Ganoderma lucidum) to investigate the effect of Fip-lti1 and Fip-lti2 expression on concanavalin A- (Con A-) induced liver oxidative injury. Both Fip-lti1 and Fip-lti2 protected the livers from Con A-induced necrosis, as evidenced by decreased serum aminotransferase levels (AST, ALT) and relieved liver histology. Levels of proinflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6) and oxidative stress (SOD, MDA) were shown to be reduced by expressing Fip-Iti1 and Fip-lti2. In addition, the hepatoprotective effect of Fip-lti1, Fip-162, and LZ-8 correlated with ameliorating the imbalance of Th1/Th2 (IFN-gamma/IL-4). The observed liver protection of Fip-lti1 and Fip-lti2 was mechanistically explored. Treatments with Fip-lti1 and Fip-lti2 regulated GATA3/T-bet expression, activated the decreased Nrf-2/HO-1 pathway, and countered the upregulated NLRP3/ASC/NF-kappa Bp65 signaling in Con A-stimulated liver injury. Nrf2 activation was shown to be involved in the mechanisms underlying the protection of Fip-lti by RNA interference. In conclusion, we identified two new fungal proteins (Fip-Iti1 and Fip-lti2) that can protect the liver from Con A-induced liver oxidative injury through the Nrf2/NF-kappa B/NLRP3/IL-1 beta pathway.

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