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

ABSTRACT: 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 (LZ-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-?, IL-1?, and IL-6) and oxidative stress (SOD, MDA) were shown to be reduced by expressing Fip-lti1 and Fip-lti2. In addition, the hepatoprotective effect of Fip-lti1, Fip-lti2, and LZ-8 correlated with ameliorating the imbalance of Th1/Th2 (IFN-?/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-?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-lti1 and Fip-lti2) that can protect the liver from Con A-induced liver oxidative injury through the Nrf2/NF-?B/NLRP3/IL-1? pathway.

SUBMITTER: Gao Y

PROVIDER: S-EPMC6526528 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Gao Yingnyu Y Wáng Ying Y Wāng Ying Y Wu Yingying Y Chen Hongyu H Yang Ruiheng R Bao Dapeng D

Oxidative medicine and cellular longevity 20190506

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 (LZ-8 from Ganoderma lucidum) to investigate the effect of Fip-lti1 and Fip-lti2 expression on concanavalin A- (Con A-) induced liver oxidative injury. ...[more]

PMID: 31198490

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Project description:Background and Aims: Acute liver failure (ALF) is a type of liver injury that is caused by multiple factors and leads to severe liver dysfunction; however, current treatments for ALF are insufficient. Magnesium isoglycyrrhizinate (MgIG), a novel glycyrrhizin extracted from the traditional Chinese medicine licorice, has a significant protective effect against concanavalin A (ConA)-induced liver injury, but its underlying therapeutic mechanism is unclear. Hence, this study aims to explore the potential therapeutic mechanism of MgIG against ConA-induced immune liver injury. Methods: ConA (20 mg/kg, i. v.) was administered for 12 h to construct an immune liver injury model, and the treatment group was given MgIG (30 mg/kg, i. p.) injection 1 h in advance. Lethality, liver injury, cytokine levels, and hepatocyte death were evaluated. The level of autophagy was evaluated by electron microscopy, RT-PCR and western blotting, and hepatocyte death was assessed in vitro by flow cytometry. Results: MgIG significantly increased the survival rate of mice and ameliorated severe liver injury mediated by ConA. The decrease in the number of autophagosomes, downregulation of LC3b expression and upregulation of p62 expression indicated that MgIG significantly inhibited ConA-induced autophagy in the liver. Reactivation of autophagy by rapamycin (RAPA) reversed the protective effect of MgIG against ConA-induced liver injury. Compared with MgIG treatment, activation of autophagy by RAPA also promoted the expression of liver inflammation markers (IL-1β, IL-6, TNF-α, CXCL-1, CXCL-2, CXCL-10, etc.) and hepatocyte death. In vitro experiments also showed that MgIG reduced ConA-induced hepatocyte death but did not decrease hepatocyte apoptosis by inhibiting autophagy. Conclusion: MgIG significantly ameliorated ConA-induced immune liver injury in mice by inhibiting autophagy. This study provides theoretical support for the ability of MgIG to protect against liver injury in clinical practice.

Dataset Information

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

Publications

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

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