Staphylococcus aureus inhibits terminal differentiation of normal human keratinocytes by stimulating interleukin-6 secretion

Background: Staphylococcus aureus (S. aureus) is found on the skin of approximately 90% of patients with atopic dermatitis and approximately 20% of apparently healthy subjects. S. aureus induces keratinocytes and immune cells to secrete immunoregulatory factors that cause epidermal barrier dysfunction in atopic skin. Objective: This study examined factors that cause epidermal permeability barrier dysfunction in skin colonized by S. aureus. Methods: We examined the effect of S. aureus on keratinocyte differentiation in the stratum corneum (SC) of in vivo skin, normal human keratinocytes (NHKs) and a reconstructed human epidermis (RHE) model. The fold change in expression of the terminal differentiation markers and the level of secreted cytokines were investigated. Results: The SC displayed decreased expression of keratin 10 (KRT 10). NHKs treated with S. aureus extracts increased expression of interleukin (IL)-6 and significantly reduced expression of the terminal differentiation markers KRT 1, KRT 10, loricrin (LOR), and filaggrin (FLG); however, the expression of basal layer markers (KRT 5, KRT 14) remained unchanged. Treatment of NHKs with an anti-IL-6 antibody in combination with IL-6 or the S. aureus extracts inhibited the decrease in KRT 10 mRNA or protein expression. After the RHEs were exposed to the S. aureus extracts, KRT 1 and KRT 10 protein levels decreased. Conclusions: These findings suggest that S. aureus inhibits the terminal differentiation of keratinocytes by stimulating IL-6 secretion.