| First Author | Jung YJ | Year | 2011 |
| Journal | J Invest Dermatol | Volume | 131 |
| Issue | 3 | Pages | 698-705 |
| PubMed ID | 21107352 | Mgi Jnum | J:182089 |
| Mgi Id | MGI:5314701 | Doi | 10.1038/jid.2010.344 |
| Citation | Jung YJ, et al. (2011) IL-1alpha stimulation restores epidermal permeability and antimicrobial barriers compromised by topical tacrolimus. J Invest Dermatol 131(3):698-705 |
| abstractText | In a previous study, we showed that barrier recovery was delayed after acute barrier disruption in the skin treated with topical calcineurin inhibitors. Tacrolimus decreases lipid synthesis and the expressions of antimicrobial peptide (AMP) and IL-1alpha in the epidermis. IL-1alpha is an important cytokine for improving barrier function, lamellar body (LB) production, and lipid synthesis in keratinocytes (KCs). We aimed to evaluate whether IL-1alpha stimulation could restore the barrier dysfunction observed in tacrolimus-treated skin. Topical imiquimod, an IL-1alpha inducer, restored the epidermal permeability barrier recovery that had been inhibited by tacrolimus treatment in human (n=15) and murine (n=10) skins, and improved stratum corneum integrity by restoring corneodosmosomes in murine skin (n=6). Imiquimod co-applied on the epidermis resulted in an increase in the production of LB and three major lipid synthesis-related enzymes, and in the expressions of mBD3, CRAMP, and IL-1alpha (n=5). Furthermore, intracutaneous injection of IL-1alpha restored permeability barrier recovery (n=6). In IL-1 type 1 receptor knockout mice, topical imiquimod was unable to restore permeability barrier recovery after tacrolimus treatment (n=21). In conclusion, IL-1alpha stimulation induced positive effects on epidermal permeability and antimicrobial barrier functions in tacrolimus-treated skin. These positive effects were mediated by an increase in epidermal lipid synthesis, LB production, and AMP expression. |
