Pimecrolimus enhances TLR2/6-induced expression of antimicrobial peptides in keratinocytes.

Journal Article (Journal Article)

Calcineurin inhibitors are potent inhibitors of T-cell-receptor mediated activation of the adaptive immune system. The effects of this class of drug on the innate immune response system are not known. Keratinocytes are essential to innate immunity in skin and rely on toll-like receptors (TLRs) and antimicrobial peptides to appropriately recognize and respond to injury or microbes. In this study we examined the response of cultured human keratinocytes to pimecrolimus. We observed that pimecrolimus enhances distinct expression of cathelicidin, CD14, and human beta-defensin-2 and beta-defensin-3 in response to TLR2/6 ligands. Some of these responses were further enhanced by 1,25 vitamin D3. Pimecrolimus also increased the functional capacity of keratinocytes to inhibit growth of Staphylococcus aureus and decreased TLR2/6-induced expression of IL-10 and IL-1beta. Furthermore, pimecrolimus inhibited nuclear translocation of NFAT and NF-kappaB in keratinocytes. These observations uncover a previously unreported function for pimecrolimus in cutaneous innate host defense.

Full Text

Duke Authors

Cited Authors

  • Büchau, AS; Schauber, J; Hultsch, T; Stuetz, A; Gallo, RL

Published Date

  • November 2008

Published In

Volume / Issue

  • 128 / 11

Start / End Page

  • 2646 - 2654

PubMed ID

  • 18496569

Pubmed Central ID

  • PMC2639780

Electronic International Standard Serial Number (EISSN)

  • 1523-1747

Digital Object Identifier (DOI)

  • 10.1038/jid.2008.135


  • eng

Conference Location

  • United States