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

Gao, Yingnyu; Wáng, Ying; Wu, Ying‐Ying; Chen, Hongyu; Yang, Runqiang; Bao, Dapeng

doi:10.1155/2019/3139689

Cited by 19 publications

(12 citation statements)

References 35 publications

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“…The results demonstrated that rFIP-mco reduced the expression levels of inflammatory cytokines by suppression of NF-kB signaling pathway. The regulating mechanism is similar to the report of Fip-lti1 and Fip-lti2 (64), in which the anti-inflammmatory properties of Fip-lti1 and Fip-lti2 were also mediated through regulating the NF-kB pathway. In the biological activity study of ACA, ACA directly activates the NF-kB signaling pathway in murine macrophages (16).…”

Section: Discussionsupporting

confidence: 85%

Identification and Functional Characterization of a Novel Immunomodulatory Protein From Morchella conica SH

Sun

Deng

et al. 2020

Front. Immunol.

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A novel fungal immunomodulatory protein (FIP) was found in the precious medical and edible mushroom Morchella conica SH, defined as FIP-mco, which belongs to the FIP family. Phylogenetic analyses of FIPs from different origins were performed using Neighbor-Joining method. It was found that FIP-mco belonged to a new branch of the FIP family and may evolved from a different ancestor compared with most other FIPs. The cDNA sequence of FIP-mco was cloned and expressed in the yeast Pichia Pastoris X33. The recombinant protein of FIP-mco (rFIP-mco) was purified by agarose Ni chromatography and determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. The protein rFIP-mco could significantly suppress the proliferation of A549 and HepG2 cells at the concentration of 15 and 5 mg/ml, respectively, and inhibited the migration and invasion of human A549 and HepG2 cells at the concentration of 15 and 30 mg/ml respectively in vitro. Further, rFIPmco can significantly reduce the expression levels of TNF-a, IL-1b, and IL-6 in the THP1 cells (human myeloid leukemia mononuclear cells). In order to explore the potential mechanism of the cytotoxicity effect of rFIP-mco on A549 and HepG2 cells, cell cycle and apoptosis assay in the two cancer cells were conducted. The results demonstrated that G0/G1 to S-phase arrest and increased apoptosis may contribute to the proliferation inhibition by rFIP-mco in the two cancer cells. Molecular mechanism of rFIP-mco's reduction effect on the inflammatory cytokines was also studied by suppression of the NF-kB signaling pathway. It showed that suppression of NF-kB signaling is responsible for the reduction of inflammatory cytokines by rFIP-mco. The results indicated the prospect of FIP-mco from M. conica SH as an effective and feasible source for cancer therapeutic studies and medical applications.

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Section: Discussionsupporting

confidence: 85%

Identification and Functional Characterization of a Novel Immunomodulatory Protein From Morchella conica SH

Sun

Deng

et al. 2020

Front. Immunol.

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“…LZ-8 suppressed effects in allogeneic tissue transplantation without side effects ( 61 ), helped increase immunity on leukopenia (low white blood cell count) induced by cyclophosphamide in mice ( 85 ), and improved both non-alcoholic fatty liver disease and early atherogenesis (fat- deposits in the arteries) because of its anti-inflammatory effect ( 86 ). FIP-lti1 and FIP-lti2 have been shown to mitigate ConA-induced liver oxidative injury ( 21 ). FIP-gmi was recently found to exert anti-inflammatory effects on neuron/glia cells ( 87 ), human fibrotic buccal mucosal fibroblasts ( 88 ), as well as intestinal mucosa and the tongue ( 89 ).…”

Section: Health-promoting Activities Of Fipsmentioning

confidence: 99%

Current Understanding of the Structure and Function of Fungal Immunomodulatory Proteins

2020

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Fungal immunomodulatory proteins (FIPs) are a group of proteins found in fungi, which are extensively studied for their immunomodulatory activity. Currently, more than 38 types of FIPs have been described. Based on their conserved structure and protein identity, FIPs can be classified into five subgroups: Fve-type FIPs (Pfam PF09259), Cerato-type FIPs (Pfam PF07249), PCP-like FIPs, TFP-like FIPs, and unclassified FIPs. Among the five subgroups, Fve-type FIPs are the most studied for their hemagglutinating, immunomodulating, and anti-cancer properties. In general, these small proteins consist of 110-125 amino acids, with a molecular weight of ∼13 kDa. The other four subgroups are relatively less studied, but also show a noticeable influence on immune cells. In this review, we summarized the protein modifications, 3-dimensional structures and bioactivities of all types of FIPs. Moreover, structure-function relationship of FIPs has been discussed, including relationship between carbohydrate binding module and hemagglutination, correlation of oligomerization and cytokine induction, relevance of glycosylation and lymphocyte activation. This summary and discussion may help gain comprehensive understanding of FIPs' working mechanisms and scope future studies.

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“…In 1992, Tiegs et al successfully established the mouse model of ALI by tail vein injection of Con A [4]. This model is accompanied by massive liver tissue necrosis, extensive inflammatory response, and prominent hepatocyte apoptosis [5]. In addition, remarkable oxidative stress injury, characterized by significant upregulation in contents of oxidative markers and significant downregulation in activities of antioxidative markers, is closely related to inflammation and Con A-mediated hepatocyte damage [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…This model is accompanied by massive liver tissue necrosis, extensive inflammatory response, and prominent hepatocyte apoptosis [5]. In addition, remarkable oxidative stress injury, characterized by significant upregulation in contents of oxidative markers and significant downregulation in activities of antioxidative markers, is closely related to inflammation and Con A-mediated hepatocyte damage [5][6][7][8]. As easy operation, low cost, well repeatability, and close to the pathological process of human viral hepatitis, Con A-induced ALI is regarded as the best experimental model for ALI research [9,10].…”

Section: Introductionmentioning

confidence: 99%

The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice

Pang

Jin

et al. 2020

Oxidative Medicine and Cellular Longevity

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Serotonin is involved in the pathological processes of several liver diseases via the regulation of inflammatory response and oxidative stress. We aimed to investigate the role of serotonin in Concanavalin A- (Con A-) induced acute liver injury (ALI). ALI was induced in C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout mice through tail vein injection of Con A (15 mg/kg body weight). Another group of TPH1 knockout ALI mice was supplied with 5-hydroxytryptophan (5-HTP) in advance to recover serotonin. The blood and liver tissues of mice were collected in all groups. Markedly increased serum levels of serotonin were identified after the injection of Con A. Increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and stronger hepatic tissue pathology were detected, suggesting that serotonin could mediate Con A-induced liver damage. Serotonin significantly facilitated the release of serum and intrahepatic inflammatory cytokines, including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17A (IL-17A), interferon-gamma (IFN-γ), and tumor necrosis-alpha (TNF-α), after the administration of Con A. In addition, serotonin significantly increased the intrahepatic levels of oxidative stress markers malonaldehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) and decreased antioxidant stress indicator glutathione (GSH) in Con A-treated mice. Additionally, serotonin promoted hepatocyte apoptosis and autophagy based on B-cell lymphoma-2 (Bcl-2), Bcl-2-asociated X protein (Bax), and Beclin-1 levels and TUNEL staining. More importantly, serotonin activated nuclear factor kappa B (NF-κB) and upregulated the hepatic expressions of high mobility group protein B1 (HMGB1), toll-like receptor-4 (TLR4), and downstream molecules in Con A-mediated liver injury. Serotonin 2A receptor was upregulated in liver tissue after Con A injection, and serotonin 2A receptor antagonist Ketanserin protected against Con A-induced hepatitis. These results indicated that serotonin has the potential to aggravate Con A-induced ALI via the promotion of inflammatory response, oxidative stress injury, and hepatocyte apoptosis and the activation of hepatic HMGB1-TLR signaling pathway and serotonin 2A receptor.

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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

Cited by 19 publications

References 35 publications

Identification and Functional Characterization of a Novel Immunomodulatory Protein From Morchella conica SH

Identification and Functional Characterization of a Novel Immunomodulatory Protein From Morchella conica SH

Current Understanding of the Structure and Function of Fungal Immunomodulatory Proteins

The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice

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