Sho-saiko-to increases calprotectin expression in human oral epithelial cells

Objectives: Oral epithelial cells prevent bacterial invasion by producing antimicrobial peptides (AMPs). We have reported that calprotectin (S100A8/S100A9), an AMP expressed within epithelial cells, inhibited invasion of Porphyromonas gingivalis. Furthermore, expression of calprotectin in human gingival keratinocytes was shown to be up-regulated by interleukin-1α(IL-1α). Sho-saiko-to (SST), a traditional Japanese herbal medicine, has immunomodulatory and anti-viral activities, and is reported to enhance levels of IL-1α in epithelial cells. In the present study, we investigated the effect of SST on the expression of calprotectin, other AMPs and IL-1α in oral epithelial cells.

Methods: Human oral epithelial cells (TR146 cells) were treated with SST (10 - 250 µg/ml). The expression of S100A8- and S100A9-specific mRNA was analyzed by Northern blotting. Calprotectin expression in TR146 cells was observed by immunofluorescent staining and quantified by ELISA. The expression of other AMPs and IL-1α genes was analyzed by RT-PCR.

Results: IL-1α was expressed in TR146 cells and specific mRNA expression was slightly increased by SST. TR146 cells expressed AMPs including calprotectin, adenomedullin, cathelicidin, cystain C, β-defensin 2, lipocalin 2 and secretory leukocyte protease inhibitor. SST (25 µg/ml) significantly increased the expression of S100A8- and S100A9-specific mRNA and calprotectin protein complex without affecting cell viability. SST also increased S100A7 expression, but showed no effect on the expression of other AMPs.

Conclusion: These results suggest that SST increases the expression of calprotectin and S100A7 in human oral epithelial cells through up-regulation of IL-1α. SST may contribute to infection control in oral cavity and be a candidate pharmacological agent for the treatment of periodontal disease.

Supported by NIH R01DE11831 (MCH) and Grants-in-Aid (#19592388) for Scientific Research from the Japan Society for the Promotion of Science.