Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 128, Issue 11, Pages 2646-2654Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2008.135
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Funding
- NIAID NIH HHS [AI052453, R37 AI052453, R01 AI052453, R01 AI052453-07] Funding Source: Medline
- NIAMS NIH HHS [R01 AR052728, R01 AR045676, R01 AR052728-04, AR45676] Funding Source: Medline
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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-1 beta. Furthermore, pimecrolimus inhibited nuclear translocation of NFAT and NF-kappa B in keratinocytes. These observations uncover a previously unreported function for pimecrolimus in cutaneous innate host defense.
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