Live Yeast Cell Derivative Induces c-fos Expression in THP-1 Monocytes

Abstract

Live Yeast Cell Derivative is a medicinal extract of Saccharomyces cerevisiae that has demonstrated efficacy in improving the rate and quality of wound healing in mouse and human systems. However, the mechanisms by which LYCD promotes healing are largely uncharacterized. In this report, we demonstrate that LYCD has effects on the transcriptional profile of the human monocytic cell line THP-1. Thirty minute exposures of THP-1 cells with LYCD induced a 6 to 44-fold, dose-dependent increase in the relative expression of the proto-oncogene c-fos in complete media containing 10% FBS or in low serum media containing 0.1% FBS. Furthermore, protein levels of c-Fos rise at 30 minutes of LYCD exposure and remained detectable for at least 120 minutes of LYCD exposure. However, the relative abundance of the c-fos transcript returned to basal levels by 120 minutes. LYCD also induced expression of c-jun with maximal expression of 3-fold at 60 minutes of exposure. Pretreatments with EGFR kinase inhibitor AG-1478 and the MEK1 inhibitor PD98059 blocked the LYCD-dependent increases in c-fos expression. Consistent with signaling through the EGFR, we have demonstrated by RT-PCR the presence of the mRNA for the EGFR (ErbB1/HER1) in THP-1 cells. Taken together these data suggest that LYCD acts through an EGFR-like cell surface receptor resulting in the activation of the EGFR kinase and the ERK1/2 signaling cascade.