FIP-fve stimulates interferon-gamma production via modulation of calcium release and PKC-alpha 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 IFN-gamma-releasing Th1 cells. However, the mechanisms of FIP-fve-mediated signal transduction in the regulation of interferon-gamma (IFN-gamma) gene expression in human peripheral 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-gamma and protein kinase C-alpha (PKC-alpha) activation in activated PBMCs, which were abolished by EGTA, nifedipine and GO6976. In conclusion, Ca2+ release and PKC-alpha activation are required for IFN-gamma production induced by FIP-fve in PBMCs.
Ou
Chu-Chyn
CC
School of Nutrition, Chung Shan Medical University, 110, Sec. 1, Chien-kuo N. Road, Taichung 40203, Taiwan.
Hsiao
Yi-Min
YM
Wu
Wen-Jun
WJ
Tasy
Gregory J
GJ
Ko
Jiunn-Liang
JL
Lin
Meei-Yn
MY
D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D055393:Flammulina / Q000737:chemistry*; D005656:Fungal Proteins / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
D002614:Chelating Agents; C547132:FIP-fve protein, Flammulina velutipes; D005656:Fungal Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D007371:Interferon-gamma; D051571:Protein Kinase C-alpha; D002118:Calcium