IL-1α stimulation restores epidermal permeability and antimicrobial barriers compromised by topical tacrolimus.
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-1α in the epidermis. IL-1α is an important cytokine for improving barrier function, lamellar body (LB) production, and lipid synthesis in keratinocytes (KCs). We aimed to evaluate whether IL-1α stimulation could restore the barrier dysfunction observed in tacrolimus-treated skin. Topical imiquimod, an IL-1α 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-1α (n=5). Furthermore, intracutaneous injection of IL-1α 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-1α 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.
Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea.
Ye-Jin
YJ
Jung
Minyoung
M
Jung
Minjeong
M
Kim
Seung-Phil
SP
Hong
Eung Ho
EH
Choi
D000287:Administration, Topical; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000382:microbiology*; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D003896:Desmosomes / Q000187:drug effects / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D053582:Interleukin-1alpha / Q000819:agonists / Q000378:metabolism / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D018345:Mice, Knockout; D008875:Middle Aged; D023421:Models, Animal; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*; D023083:beta-Defensins / Q000378:metabolism
D000634:Aminoquinolines; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C422950:DEFB103A protein, human; D007166:Immunosuppressive Agents; D053582:Interleukin-1alpha; D017472:Receptors, Interleukin-1; D023083:beta-Defensins; C540070:beta-defensin 3, mouse; D000077271:Imiquimod; D016559:Tacrolimus