Saliva induces expression of antimicrobial peptides and promotes intracellular killing of bacteria in keratinocytes by epidermal growth factor receptor transactivation

Br J Dermatol. 2017 Feb;176(2):403-412. doi: 10.1111/bjd.14883. Epub 2017 Jan 24.

Abstract

Background: Wounds in the oral cavity, constantly exposed to both saliva and bacteria, heal quickly without infection. Furthermore, during licking of skin wounds, saliva promotes wound healing and plays a role in keeping the wound free of infection.

Objectives: To investigate whether saliva induces expression of antimicrobial peptides (AMPs) in human epidermal keratinocytes and whether saliva promotes clearance of intracellular bacteria in these cells.

Methods: Expression of AMPs was investigated in the oral mucosa and ex vivo injured skin by immunohistochemistry. Human beta-defensin-3 expression was investigated in epidermal keratinocytes after saliva stimulation, using real-time polymerase chain reaction and immunofluorescence.

Results: We found higher expression of AMPs in the oral mucosa than in the epidermis. Saliva accelerated the injury-induced expression of AMPs in human skin ex vivo and was a potent inducer of the expression of AMPs in epidermal keratinocytes. The expression of AMPs was induced by metalloproteinase-dependent epidermal growth factor receptor (EGFR) transactivation mediated by a salivary lipid. Saliva increased the intracellular clearance of Staphylococcus aureus in keratinocytes through EGFR activation.

Conclusions: These findings suggest a previously unreported role of saliva in innate immunity and demonstrate for the first time that saliva induces gene expression in epidermal keratinocytes.

MeSH terms

  • Antimicrobial Cationic Peptides / metabolism*
  • Cells, Cultured
  • ErbB Receptors / physiology*
  • Humans
  • Keratinocytes / metabolism
  • Keratinocytes / microbiology*
  • Lipids / physiology
  • Mouth Mucosa / metabolism
  • Phagocytosis / physiology
  • Saliva / physiology*
  • Skin / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Lipids
  • EGFR protein, human
  • ErbB Receptors