Expression of S100A8 is induced by interleukin‑1α in TR146 epithelial cells through a mechanism involving CCAAT/enhancer binding protein β.

Abstract

Calprotectin in mucosal epidermal keratinocytes has an important role in fighting microbial infections. S100A8 belongs to the S100 protein family and is a subunit of calprotectin (heterodimer complex of S100A8/A9). Interleukin‑1α (IL‑1α) is one of the cytokines produced by oral keratinocytes. The primary aims of the present study were to investigate the effect of IL‑1α on the expression of S100A8 and its underlying molecular mechanism in oral epithelial cells. Determining the molecular mechanism of the induced expression of S100A8 by IL‑1α aims to improve current understanding of the roles of calprotectin during the infection of mucosal epithelial cells. The expression analysis indicated that IL‑1α significantly induced the expression of S100A8 in human TR146 epithelial cells at the mRNA and protein levels, respectively. The reporter assay demonstrated that the upregulatory effect of S100A8 induced by IL‑1α was dependent on the S100A8 promoter specific region (‑165/‑111). The results of electrophoresis mobility shift assay and chromatin immunoprecipitation assay also demonstrated that the CCAAT/enhancer binding protein β (C/EBPβ) binding site (‑113/‑109) in the S100A8 promoter region was involved into the upregulatory effect on the expression of S100A8 induced by IL‑1α. Taken together, these results suggested that the activation of the expression of S100A8 induced by IL‑1α in TR146 epithelial cells involves a mechanism by which the binding activity of C/EBPβ to the specific site (‑113/‑109) of the S100A8 promoter is increased.