Staphylococcus aureus induces IL-8 expression through its lipoproteins in the human intestinal epithelial cell, Caco-2

• Staphylococcus aureus induces IL-8 production in the human intestinal epithelial cell Caco-2.
• S. aureus lipoproteins and Pam2CSK4 mimicking Gram-positive bacterial lipoproteins also induce IL-8 expression in Caco-2.
• Peptidoglycan or lipoteichoic acid of S. aureus hardly induces IL-8 expression in Caco-2.
• Lipoprotein-deficient S. aureus mutant fails to induce IL-8 expression in Caco-2.
• Lipoprotein might be responsible for S. aureus-induced IL-8 expression in the human intestinal epithelial cells.

Staphylococcus aureus can cause the intestinal inflammatory diseases. However, little is known about the molecular mechanism of S. aureus infection in the intestine. In the present study, we investigated whether S. aureus could stimulate human intestinal epithelial cells triggering inflammation. When the human intestinal epithelial cell-line, Caco-2, and the primary colon cells were stimulated with ethanol-inactivated S. aureus, IL-8 expression was induced in a dose-dependent manner. The inactivated S. aureus preferentially stimulated Toll-like receptor (TLR) 2 rather than TLR4. Lipoproteins, lipoteichoic acid (LTA), and peptidoglycan (PGN) are considered as potential TLR2 ligands of S. aureus. Interestingly, S aureus lipoproteins and Pam2CSK4 mimicking Gram-positive bacterial lipoproteins, but not LTA and PGN of S. aureus, significantly induced IL-8 expression in Caco-2 cells. Furthermore, lipoprotein-deficient S. aureus mutant strain failed to induce IL-8 production. Collectively, these results suggest that S. aureus stimulates the human intestinal epithelial cells to induce the chemokine IL-8 production through its lipoproteins, potentially contributing the development of intestinal inflammation.