INHIBITION OF TNF-α AND IL-6 PRODUCTION BY AUCUBIN THROUGH BLOCKADE OF NF-κB ACTIVATION IN RBL-2H3 MAST CELLS
Abstract Antigen (Ag)-stimulated mast cells induce synthesis and production of cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-6 with proinflammatory and immune regulatory properties. Expression of TNF-α and IL-6 was regulated by a transcription factor, nuclear factor (NF)-κB. The iridoid glycoside, aucubin, has been found as a natural constituent of many traditional oriental medicinal plants. We studied the effect of aucubin on the TNF-α and IL-6 expression in Ag-stimulated rat basophilic leukemia (RBL)-2H3 mast cells. We show that aucubin inhibited Ag-induced TNF-α and IL-6 production and expression in a dose-dependent manner with IC50 of 0.101 and 0.19 μg/ml, respectively. Maximal inhibition of TNF-α and IL-6 production was 73±4.3% and 88.8±5%, respectively. Aucubin also inhibited Ag-induced nuclear translocation of p65 subunit of NF-κB and degradation of IκBα. Inhibition of NF-κB activation by aucubin might be specific since activator protein-1 binding activity was not affected. In conclusion, these results suggest that aucubin is a specific inhibitor of NF-κB activation in mast cells, which might explain its beneficial effect in the treatment of chronic allergic inflammatory diseases.