Background and Objective: Oral epithelial cells help to prevent against bacterial infection in the oral cavity by producing antimicrobial peptides (AMPs). A broad-spectrum AMP, calprotectin (a complex of S100A8 and S100A9 proteins), is expressed by oral epithelial cells and is up-regulated by interleukin-1 alpha (IL-1 alpha). Shosaikoto (SST) is a traditional Japanese herbal medicine that has immunomodulatory effects and is reported to enhance the levels of IL-1 alpha in epithelial cells. The purpose of this study was to investigate the effect of SST on the expression of calprotectin and other AMPs through the regulation of IL-1 alpha in oral epithelial cells. Material and Methods: Human oral epithelial cells (TR146) were cultured with SST (at concentrations ranging from 10 to 250 mu g/mL) in the presence or absence of anti-IL-1 alpha or IL-1 receptor antagonist. The expression of S100A8- and S100A9-specific mRNAs was examined by northern blotting. Calprotectin expression and IL-1 alpha secretion were investigated by immunofluorescent staining or ELISA. The expression of other AMPs and IL-1 alpha was analyzed by RT-PCR and by quantitative real-time PCR. Results: Shosaikoto (25 mu g/mL) significantly increased the expression of S100A8- and S100A9-specific mRNAs and calprotectin protein. Shosaikoto increased S100A7 expression, but had no effect on the expression of other AMPs. The expression of IL-1 alpha-specific mRNA and its protein were slightly increased by SST. A neutralizing antibody against IL-1 alpha or IL-1 receptor antagonist inhibited SST up-regulated S100A8/S100A9 mRNA expression. Conclusion: These results suggest that SST increases the expression of calprotectin and S100A7 in oral epithelial cells. In response to SST, up-regulation of calprotectin may be partially induced via IL-1 alpha.