Resveratrol Alters Proliferative Responses and Apoptosis in Human Activated B Lymphocytes in Vitro

摘要

We hypothesized that the phytochemicals resveratrol, quercetin, and kaempferol would modulate B lymphocyte proliferation, Ig synthesis, and apoptosis after activation. Peripheral blood mononuclear cells (PBMC) were isolated from 12 healthy adult human volunteers and incubated with pokeweed mitogen plus 0, 2, 5, and 10 µmol/L resveratrol, quercetin, or kaempferol. After 6 d, CD19+ B cells were analyzed for proliferation, B cell lymphoma-2 (Bcl-2) expression, and activation of caspase-3 using flow cytometry. After 8 d, cell supernatants were collected and IgM and IgG were measured by ELISA. Resveratrol at a concentration of 5 µmol/L increased the percentage of CD19+ cells compared with mitogen only-stimulated cells (P < 0.01), and a trend for increased proliferation was observed for cells treated with 0, 2, and 5 µmol/L resveratrol (P-trend = 0.01). However, 10 µmol/L resveratrol inhibited proliferation of B lymphocytes (P < 0.01). Expression of Bcl-2 and caspase-3 activation increased in B cells treated with 10 µmol/L resveratrol compared with mitogen alone (P < 0.01), and trends for dose-responsive increases in Bcl-2 expression and caspase-3 activation were observed (P-trend < 0.0001). Differences in IgM and IgG production were not observed for PBMC treated with resveratrol. Kaempferol at 10 µmol/L slightly inhibited proliferative responses (P < 0.05) but did not affect B cell function or apoptosis. Quercetin did not alter B cell proliferation, function, or apoptosis. These data show that human B lymphocyte proliferation and apoptosis are modified by physiological concentrations of resveratrol and suggest that exposure of human B cells to resveratrol may increase survival by upregulating Bcl-2.