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

• Published in: Journal of dermatological science 2014-04, Vol.74 (1), p.64-71
• Main Authors: Son, Eui Dong, Kim, Hyoung-June, Park, Taehun, Shin, Kyeho, Bae, Il-Hong, Lim, Kyung-Min, Cho, Eun-Gyung, Lee, Tae Ryong
• Format: Article
• Language: English
• Subjects: Adult; Biofilms; Cell Differentiation; Cells, Cultured; Dermatitis, Atopic - metabolism; Dermatology; Epidermal differentiation; Epidermis - metabolism; Epidermis - microbiology; Gene Expression Regulation, Bacterial; Humans; Interleukin 6; Interleukin-6 - metabolism; Intermediate Filament Proteins - metabolism; Keratin-1 - metabolism; Keratin-10 - metabolism; Keratinocytes - cytology; Keratinocytes - metabolism; Keratinocytes - microbiology; Male; Membrane Proteins - metabolism; Middle Aged; Normal human keratinocytes; Skin barrier; Staphylococcus aureus; Staphylococcus aureus - metabolism
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2013.12.004

Abstract 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.