title: Staphylococcus aureus inhibits terminal differentiation of normal human keratinocytes by stimulating interleukin-6 secretion.
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.
authors.affiliation: AmorePacific Corp/R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: Eui Dong
authors.initials: ED
authors.lastname: Son
authors.affiliation: AmorePacific Corp/R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: Hyoung-June
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: AmorePacific Corp/R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: Taehun
authors.initials: T
authors.lastname: Park
authors.affiliation: AmorePacific Corp/R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: Kyeho
authors.initials: K
authors.lastname: Shin
authors.affiliation: AmorePacific Corp/R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: Il-Hong
authors.initials: IH
authors.lastname: Bae
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
authors.affiliation: AmorePacific Corp/R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea. Electronic address: egcho@amorepacific.com.
authors.forename: Eun-Gyung
authors.initials: EG
authors.lastname: Cho
authors.affiliation: AmorePacific Corp/R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea. Electronic address: TRLee@amorepacific.com.
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
mesh_terms: D000328:Adult; D018441:Biofilms; D002454:Cell Differentiation; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism / Q000382:microbiology; D000091344:Filaggrin Proteins; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053556:Keratin-1 / Q000378:metabolism; D053550:Keratin-10 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D007381:Intermediate Filament Proteins; C491616:KRT1 protein, human; C507493:KRT10 protein, human; D053556:Keratin-1; D008565:Membrane Proteins; C064554:loricrin; D053550:Keratin-10
keywords: Epidermal differentiation; Interleukin 6; Normal human keratinocytes; Skin barrier; Staphylococcus aureus