Cordyceps militaris induces the IL-18 expression via its promoter activation for IFN-γ production

Ethnopharmacological relevanceCordyceps militaris, one of traditional herbal ingredient in oriental medicine, has been known to promote anticancer and immunomodulatory activities in vitro and in vivo. However, the biological mechanism of anticancer activity has been unknown.ObjectiveTo investigate the effect of Cordyceps militaris extract on expression of interferon gamma (IFN-γ) through interlukin-18 (IL-18) induction and its biological mechanism in vitro and in vivo.Materials and methodsMice were administrated orally with solution extracted from Cordyceps militaris. The transcription level of IL-18 and IFN-γ production were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RAW 264.7 cells were transiently transfected with pCATp1 and pCATp2 for IL-18 promoter functional analysis.ResultsCordyceps militaris extracts treatment significantly induced level of IL-18 transcription in mouse brain and liver and enhanced IL-18 transcription level and activated the IFN-γ production in RAW 264.7 cells. Furthermore, Cordyceps militaris extract led to increase the activity of pCATp1 construct containing the 5′ franking region of IL-18 promoter in RAW 264.7 cells.ConclusionCordyceps militaris extract induced IL-18 mRNA level via enhancing of P1 promoter region result in activation of IFN-γ production, indicating its potential as an immune activator or anticancer drug.