Immunosuppressive and regulatory mechanism of artesunate / 中国药学杂志

ABSTRACT

OBJECTIVE: To determine the immunoregulatory mechanism of artesunate both in vitro and in vivo. METHODS: The immunosuppressive action of artesunate was investigated through lymphocyte proliferation and cytotoxicity was also detected in vitro. The delayed-type hypersensitivity (DTH) model in mice was used for the investigation of artesunate in vivo. The mRINA expression of T-bet, GATA-3, ROR-γt and IL-17 gene was determined by RT-PCR. ELISA assay was used to detect the contents of IL-17, and Western blot assay was applied to investigate the p38 mitogen-activated protein kinase (MAPK) activation. RESULTS: Artesunate could inhibit ConA-induced T lymphocyte and LPS-induced B lymphocyte proliferation in vitro significantly, which also showed lower toxicity than dexamethasone. Meanwhile, topical application of artesunate could both suppress the increase on ear thickness in DTH mice and inhibit the thymus index and spleen index. Furthermore, artesunate was found to regulate the expression level of transcription factor (T-bet in the GATA-3), and down-regulate ROR-γt and IL-17 expression. What's more, the production of IL-17 was decreased in ear tissue. Finally, artesunate was observed to decrease p38 mitogen-activated protein kinase (MAPK) activation. CONCLUSION: Artesunate, as a new immunomodulatory agents, might contribute to performing immunosuppression through modulating the balance of treg/Th17 and anti-inflammatory.