Yuh-Chi Kuo

Activation and proliferation signals in primary human T lymphocytes inhibited by ergosterol peroxide isolated from Cordyceps cicadae

Effects of ergosterol peroxide (C28H44O3; Cpd 6A) from Cordyceps cicadae on phytohemagglutinin (PHA)‐stimulated cell proliferation were studied in primary human T cells. The results showed that Cpd 6A suppressed T‐cell proliferation for about 24 h after stimulation with PHA. Cell cycle analysis indicated that Cpd 6A arrested the cell cycle progression of activated T cells from the G1 transition to the S phase. To localize the point in the cell cycle where arrest occurred, a set of key regulatory events leading to the G1/S boundary, including the expression of cyclins D2, E, A1, and B1, interleukin (IL)‐2, IL‐4, interferon‐γ (IFN‐γ), and activating protein‐1 (AP‐1), was examined. Cpd 6A suppressed, in activated T lymphocytes, the production and mRNA expression of cyclin E, IL‐2, IL‐4, IL‐10, and IFN‐γ in a dose‐dependent manner. Expression of AP‐1 proteins, consisting of c‐Fos and c‐Jun, in activated T lymphocytes was decreased by Cpd 6A. The kinetic study indicated that the inhibitory effects of Cpd 6A on IL‐2 mRNA expressed in T cells might be related to blocking c‐Fos protein synthesis. T‐cell proliferation after Cpd 6A treatment was partially restored by addition of IL‐2, IL‐4, and IFN‐γ. These suppressant effects of Cpd 6A on T‐cell proliferation, activated by PHA, appeared to be mediated, at least in part, through the inhibition of early gene transcripts, especially those of cyclin E, IFN‐γ, IL‐2, and IL‐4, and by arresting cell cycle progression in the cells.

Immunomodulatory functions of extracts from the Chinese medicinal fungus Cordyceps cicadae

The effects of Cordyceps cicadae extracted fractions on human mononuclear cells (HMNC) proliferation were determined by tritiated thymidine uptake. The results indicated that aqueous methanol (50%) extracts of C. cicadae ascocarps portion (CC-1-2) enhanced HMNC proliferation activated with phytohemagglutinin (PHA) with an EC(50) of 13.8+/-4.6 micro g/ml. By contrast, the methanol (100%) extracts of C. cicadae insect-body portion (CC-2-1) suppressed HMNC proliferation stimulated by PHA with an IC(50) of 32.5+/-5.2 micro g/ml. Cell viability test indicated that inhibitory effects of CC-2-1 on HMNC proliferation were not through direct cytotoxicity. The action mechanisms of CC-1-2 and CC-2-1 may involve the regulation of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production in HMNC. Since CC-2-1 suppressed IL-2 and IFN-gamma production in HMNC induced with PHA. The CC-1-2 enhanced IL-2 and IFN-gamma production of HMNC stimulated with PHA in a concentration dependent manner. Therefore, the results demonstrated that C. cicadae contained growth modulators for HMNC.

Suberosin inhibits proliferation of human peripheral blood mononuclear cells through the modulation of the transcription factors NF‐AT and NF‐κB

Extracts of Plumbago zeylanica containing suberosin exhibit anti‐inflammatory activity. We purified suberosin from such extracts and studied its effects on a set of key regulatory events in the proliferation of human peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin (PHA).