Differential suppression of epidermal antimicrobial protein expression in atopic dermatitis and in EFAD mice by pimecrolimus compared to corticosteroids

Exp Dermatol. 2011 Oct;20(10):783-8. doi: 10.1111/j.1600-0625.2011.01322.x. Epub 2011 Jun 24.

Abstract

It has been suggested that the increased rate of bacterial infection in atopic dermatitis (AD) may be caused by reduced antimicrobial protein (AMP) expression. We were interested whether common treatments in AD affect antimicrobial defense. We investigated the effects of topically applied corticosteroids betamethasone valerate (BV) and triamacinolone acetonide (TA) and those of the calcineurin inhibitor pimecrolimus for 3 weeks on AMP expression in AD. BV and TA treatment in AD led to a significant reduction in AMP expression; protein expression of human beta-defensins (hBD)-2 and hBD-3, psoriasin, RNase 7 and cathelicidin LL-37 was below the level in skin of healthy controls. After pimecrolimus treatment, AMP expression was also reduced but less compared to BV and TA; the expression levels of hBD-2, psoriasin and RNase 7 still remained above the control levels. In essential fatty acid-deficient (EFAD) mice, a model of chronic skin barrier disease with inflammation, expression of the mouse beta-defensins mBD-1, mBD-3 and mBD-14 (orthologues for hBD-1, hBD-2 and hBD-3, respectively), was reduced by both treatments, again more pronounced by BV compared to pimecrolimus. In summary, we found that treatment for AD with corticosteroids in human skin and EFAD mice caused a strong reduction in AMPs; reduction was less with pimecrolimus. This result may explain the clinical observation that prolonged treatment with topical corticosteroids sometimes leads to bacterial infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / adverse effects*
  • Animals
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism*
  • Base Sequence
  • Betamethasone Valerate / adverse effects
  • Calcineurin Inhibitors
  • Case-Control Studies
  • DNA Primers / genetics
  • Dermatitis, Atopic / complications
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / metabolism*
  • Disease Models, Animal
  • Fatty Acids, Essential / deficiency
  • Gene Expression / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Hairless
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Skin Diseases, Bacterial / etiology
  • Tacrolimus / adverse effects
  • Tacrolimus / analogs & derivatives*
  • Triamcinolone Acetonide / adverse effects
  • beta-Defensins / genetics
  • beta-Defensins / metabolism

Substances

  • Adrenal Cortex Hormones
  • Antimicrobial Cationic Peptides
  • Calcineurin Inhibitors
  • DNA Primers
  • Fatty Acids, Essential
  • RNA, Messenger
  • beta-Defensins
  • pimecrolimus
  • Betamethasone Valerate
  • Triamcinolone Acetonide
  • Tacrolimus