Injury downregulates the expression of the human cathelicidin protein hCAP18/LL-37 in atopic dermatitis

Exp Dermatol. 2010 May;19(5):442-9. doi: 10.1111/j.1600-0625.2009.00918.x. Epub 2009 Jul 23.

Abstract

Reduced production of antimicrobial peptides was proposed to contribute to susceptibility for skin infections in atopic dermatitis (AD). Focusing on the human cathelicidin protein, hCAP18, the aim of the present study was to explore whether reduced hCAP18 expression is a constitutive trait in AD and if established inducers affect the expression of hCAP18 in the skin of AD. First, we compared levels of hCAP18 mRNA between lesional skin in AD and psoriasis and verified significantly lower expression of hCAP18 mRNA in AD. In non-lesional skin, however, there was no difference between AD, psoriasis and healthy, indicating that there is no constitutive defect in the production of hCAP18 in AD patients. In healthy skin, hCAP18 was reported to be rapidly induced following wounding and here we verified this pattern in healthy controls and in psoriasis. In AD lesions, however, the expression of hCAP18 mRNA was markedly suppressed following wounding. Obviously, the inflammation in AD lesions neutralizes the expected induction of hCAP18 and even induces suppression. Notably, the mechanism to upregulate hCAP18 following vitamin D treatment was functional in lesional as well as in non-lesional AD indicating that the CAMP gene is normally regulated in this respect. In addition, cultured primary keratinocytes from non-lesional skin of psoriasis, AD and healthy skin, upregulated hCAP18mRNA following treatment with vitamin D. Itching is a hallmark of AD and scratching inevitably injures the skin. Failure to upregulate hCAP18 in eczema following injury is likely to affect antimicrobial protection and tissue repair in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimicrobial Cationic Peptides
  • Cathelicidins / genetics*
  • Cathelicidins / metabolism*
  • Cells, Cultured
  • Cholecalciferol / pharmacology
  • Dermatitis, Atopic / genetics*
  • Dermatitis, Atopic / metabolism*
  • Down-Regulation / drug effects
  • Down-Regulation / genetics*
  • Female
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Middle Aged
  • Psoriasis / genetics
  • Psoriasis / metabolism
  • Skin / drug effects
  • Skin / injuries
  • Skin / metabolism
  • Wounds and Injuries / genetics*
  • Wounds and Injuries / metabolism*
  • Young Adult

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Lipopolysaccharide Receptors
  • CAP18 lipopolysaccharide-binding protein
  • Cholecalciferol