Characterization of a novel fungal immunomodulatory protein, FIP-SJ75 shuffled from Ganoderma lucidum , Flammulina velutipes and Volvariella volvacea

Abstract

FIP-SJ75, a novel fungal immunomodulatory protein gene, was shuffled from the genes of three different mushroom species: Ganoderma lucidum, Flammulina velutipes, and Volvariella volvacea. Based on the expression of FIP-SJ75 gene in Escherichia coli, recombinant FIP-SJ75 (rFIP-SJ75) was routinely confirmed, consisting of 115 amino acids, and six peptides were identified by LC/Q-TOF MS with a coverage rate of 84.3%. Bioactivity assay in vitro indicated that rFIP-SJ75 promoted the proliferation of RAW264.7 cells at a range of 1-8 μg/mL, and significantly activated RAW264.7 cells in a dose-dependent manner. Real-time PCR revealed rFIP-SJ75 obviously promoted pro-inflammatory genes (TNF-α and IL-6), but reduced the expression of anti-inflammatory genes (IL-10 and TGF-β1) at the transcriptional level. These data implied that rFIP-SJ75 possessed immunomodulatory activity in macrophages by promoting macrophage M1 polarization and initiating pro-inflammatory responses, which could lay the foundation for rFIP-SJ75 to become a stable immunomodulator resource for further research and potential applications.

Natural Bioactive Compounds from Fungi as Potential Candidates for Protease Inhibitors and Immunomodulators to Apply for Coronaviruses

“…Many drugs are known to be immunomodulatory substances because they have significant clinical efficacy for altering host responses in the therapy of viral and bacterial infections [111][112][113][114]. Various edible mushrooms have been studied for many years in terms of the effects of their metabolites in boosting immune responses and treating infectious [115][116][117][118]. The principal immunomodulatory effect of active substances derived from mushrooms is to stimulate immune effector cells such as T cells, cytotoxic T lymphocytes (CTL), dendritic cells (DCs), lymphocytes, macrophages and natural killer (NK) cells, resulting in cytokine expression and secretion including interleukins (ILs), tumor necrosis factor-alpha (TNF)-α, and interferon-gamma (INF)-γ [119,120].…”

Current Understanding of the Structure and Function of Fungal Immunomodulatory Proteins

“…However, the exact underlying mechanism of DCs ( 58 , 73 ) and macrophages ( 62 ) activation by LZ-8 still needs to be further explored, especially its supposed TLR4 binding, since minor lipopolysaccharide (LPS) contamination could cause similar results in DCs and macrophages ( 74 , 75 ). FIP-SJ75, which is a chimera composed of LZ-8, FIP-fve and FIP-vvo ( 19 ), triggered similar cytokine expression profiles in macrophages as seen for LZ-8 (shown in Table 3 ). Its underlying mechanism was still unknown, which needs further investigation.…”

The Enhancing Effect of Fungal Immunomodulatory Protein-Volvariella Volvacea (FIP-vvo) on Maturation and Function of Mouse Dendritic Cells

“…In this study, the recombinant FIP-vvo proteins can enhance DC maturation and function the same as the natural FIP-vvo. Furthermore, recent studies have demonstrated that FIP-SJ75, reconstituted FIP from G. lucidum, F. velutipes, and V. volvacea, has increased immunomodulatory function on RAW264.7 macrophages [40]. Therefore, it is worthwhile to keep investigating and optimizing these FIPs.…”

“…velutipes , and V . volvacea , has increased immunomodulatory function on RAW264.7 macrophages [ 40 ]. Therefore, it is worthwhile to keep investigating and optimizing these FIPs.…”