The Possible Role of PD-1 Protein in Ganoderma lucidum–Mediated Immunomodulation and Cancer Treatment

Background: Ganoderma lucidum has been used in Chinese medicine for thousands years to improve health and to promote longevity. One important function of G lucidum is to modulate the immune system. However, the underlying mechanism is not well understood. Programmed cell death protein 1 (PD-1) is a cell surface protein present in certain immune cells (eg, B- and Tcells) and plays an important role in modulating the immune response. The role of PD-1 protein in G lucidum–mediated immunomodulation is unknown. Methods: Cultured human Blymphocytes and extract prepared from G lucidum spores (GLE) were used to determine PD-1 protein in G lucidum–mediated immunomodulation. Both western blotting and immunofluorescence (IF) microscopy assays were used to determine the effect of GLE treatment on PD-1 protein expression. A reverse transcription-based quantitative polymerase chain reaction (real-time PCR) assay was used to determine the effect of GLE on transcription of pdcd-1 gene. Results: Both our western blotting and IF staining results demonstrated great reduction in PD-1 protein and in proportion of PD-1+ cells in these B-lymphocytes. Our real-time PCR results indicated that this PD-1 protein reduction was not caused by a transcriptional inhibition of the gene. In addition, our western blotting study further revealed that the GLE treatment caused an increase in expression of CCL5 chemokine in the cultured B-lymphocytes. Conclusions: PD-1 protein is an important target of G lucidum–mediated immunomodulation. G lucidum and its bioactive compounds can be developed into novel immunomodulators for prevention and treatment of cancer and many other diseases.