The early signaling pathway of live yeast cell derivative in THP-1 monocytes

Live yeast cell derivative (LYCD) is a medicinal yeast extract that has been used in the treatment of burns, wounds and hemorrhoids for over 70 years. It has been shown to enhance the closure of skin wounds in diabetic mice by increasing inflammation, angiogenesis, formation of granulation tissue and epithelial migration. An active fraction of LYCD has been identified as a mixture of peptides ranging in size from 5 kDA to 17 kDA. Despite its widespread use over many years, understanding of the mechanism by which LYCD acts to effect tissue repair responses is very limited. In this study, we have used a human monocyte-derived cell line, THP-1, as a representative of the inflammatory component of the wound healing process. We have identified two of the earliest responses to LYCD as an increase in cytoplasmic free calcium ([Ca2+]i) and the transcripts for c-fos. We have found that the increase in [Ca2+]i is both necessary and sufficient to account for the LYCD-induced elevation of c-fos. Furthermore, we have shown that the signaling pathway by which LYCD elevates [Ca2+]i involves both mobilization of Ca2+ from intracellular stores and influx of Ca2+ from the extracellular medium. Mobilization of store Ca2+ occurs first via activation of phospholipase C and this is followed by influx through activation of store operated calcium channels. These results constitute the first delineation of the early steps of the LYCD signaling pathway.