FIP-fve stimulates interferon-gamma production via modulation of calcium release and PKC-α activation

Fungal immunomodulatory protein, FIP-fve, has been isolated from Flammulina velutipes, and its immunomodulatory effects are believed to be associated with the enhanced activation of IFNγ-releasing Th1 cells. However, the mechanisms of FIP-fve-mediated signal transduction in the regulation of interferon-gamma (IFN-γ) gene expression in human perkipheral blood mononuclear cells (PBMCs) are still poorly understood. Using fluo-3 AM, we found that FIP-fve induces a rapid elevation in calcium concentration. ELISA, RT-PCR and Western blot assays demonstrated significant increases in the production and mRNA expression of IFN-γ and protein kinase C-alpha (PKC-α) activation in activated PBMCs, which were abolished by EGTA, nifedipine and GÖ6976. In conclusion, Ca2+ release and PKC-α activation are required for IFN-γ production Induced by FIP-fve in PBMCs.