IL-1 receptor regulates S100A8/A9-dependent keratinocyte resistance to bacterial invasion

Previously, we reported that epithelial cells respond to exogenous interleukin (IL)-1 alpha by increasing expression of several genes involved in the host response to microbes, including the antimicrobial protein complex calprotectin (S100A8/A9). Given that S100A8/A9 protects epithelial cells against invading bacteria, we studied whether IL-1 alpha augments S100A8/A9-dependent resistance to bacterial invasion of oral keratinocytes. When inoculated with Listeria monocytogenes, human buccal epithelial (TR146) cells expressed and released IL-1 alpha. Subsequently, IL-1 alpha-containing media from Listeria-infected cells increased S100A8/A9 gene expression in naive TR146 cells an IL-1 receptor (IL-1R)-dependent manner. Incubation with exogenous IL-1 alpha decreased Listeria invasion into TR146 cells, whereas invasion increased with IL-1R antagonist. Conversely, when S100A8/A9 genes were knocked down using short hairpin RNA (shRNA), TR146 cells responded to exogenous IL-1 alpha with increased intracellular bacteria. These data strongly suggest that infected epithelial cells release IL-1 alpha to signal neighboring keratinocytes in a paracrine manner, promoting S100A8/A9-dependent resistance to invasive L. monocytogenes