| Summary: | 博士 === 國立陽明大學 === 藥理學研究所 === 94 === T cell-dependent immune responses play important roles in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Nelumbo nucifera is a useful edible and medicinal plant for the treatment of diarrhea, tissue inflammation, and hemostasis. A previous study conducted by our laboratory showed that (S)-armepavine (C19H23O3N; MW313) from N. nucifera inhibited the proliferation of human blood mononuclear cells (PBMCs) activated with phytohemagglutinin (PHA). Therefore, the present study examined the immune modulatory actions of (S)-armepavine on MRL-lpr/lpr mice in vivo and PBMCs in vitro. MRL-lpr/lpr mice treated orally with (S)-armepavine (5 or 10 mg/kg/day) for 6 weeks could prevent lymphadenopathy and elongate life span. It seemed to be mediated by inhibition of splenocytes proliferation, suppression of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10), and interferon-�� (IFN-��) genes expression, reduction of glomerular hypercellularity and immune complexes deposition, decrease of urinary protein, anti-double stranded DNA autoantibody and anti-small nuclear ribonuclear protein antibody production, and impairments of cytokines production. The in vitro results showed that (S)-armepavine (25, 50, and 100 �嵱) suppressed inducible T cells kinase and phospholipase C�� phosphorylation in a phosphoinositide 3-kinase (PI3K)-dependent manner, but (S)-armepavine had no effect on lymphocyte-specific kinase or ��-associated protein-70 phosphorylation. Through blocking the activation of PI3K, (S)-armepavine inhibited its downstream signaling such as Ca2+, protein kinase C, nuclear factor of activated T cells, nuclear factor �羠, and activator protein-1 expression in PHA-activated PBMCs. The study also showed (S)-armepavine had no direct cytotoxicity, but attenuated the mRNA and protein expression of IL-2 and IFN-��, and thereby suppressed the proliferation of PHA-activated PBMCs. By blocking cell proliferation and inflammatory mediators production of T cells, (S)-armepavine may to be developed as a potential immunosuppressive agent for the management of autoimmune disease like SLE.
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