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• W2020093059 abstract "Our bodies are equipped with a variety of mechanisms to optimize survival. A keratinized epidermis and the complex “brick and mortar” construction are first lines of defense against invading organisms. When the stratum corneum and epidermal architecture are disrupted, a second line of defense, the innate immune system, is upregulated. Previous studies have shown that topically applied tacrolimus slows restoration of the epidermal barrier following tape stripping and also reduces the innate immune reactivity, which ordinarily serves in antimicrobial defense (Kim et al., 2010Kim M. Jung M.Y. Hong S.P. et al.Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function.Exp Dermatol. 2010; 19: 501-510Crossref PubMed Scopus (50) Google Scholar). Tacrolimus is used commonly for patients with atopic dermatitis (AD), which may involve barrier disruption, cutaneous infections, and downregulated innate immune reactivity (Howell, 2007Howell M.D. The role of human beta defensins and cathelicidins in atopic dermatitis.Curr Opin Allergy Clin Immunol. 2007; 7: 413-417Crossref PubMed Scopus (55) Google Scholar). In randomized trials, tacrolimus improves the skin of patients with AD without increasing the frequency of bacterial infections. By contrast, viral skin infections have been reported to be increased (Ashcroft et al., 2005Ashcroft D.M. Dimmock P. Garside R. et al.Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomized controlled trials.BMJ. 2005; 330: 516Crossref PubMed Scopus (225) Google Scholar). Consequently, the effects of tacrolimus on the epidermal barrier may be important. To examine mechanisms of tacrolimus-impaired barrier restoration, Jung and Kim, 2011Jung M. Kim M. et al.IL-1α stimulation restores epidermal permeability and antimicrobial barriers compromised by topical tacrolimus.J Invest Dermatol. 2011; 131: 698-705Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar et al. (2011, this issue) evaluated the role of IL-1 in the stimulation of barrier-function recovery. Working with both mice and human volunteers, these researchers demonstrated a role for IL-1α signaling in tacrolimus-induced permeability barrier dysfunction. Intracutaneous injection of IL-1α significantly improved barrier recovery of tacrolimus-treated murine skin; however, this improvement was not observed in transgenic mice that lacked the IL-1 receptor. Interestingly, imiquimod, which induces IL-1α, accelerated barrier recovery in tacrolimus-treated skin, increased epidermal lipid production via upregulation of enzymes important in lipid synthesis, and increased mRNA levels of molecules involved in innate immunity—specifically, mouse β-defensin 3 and cathelin-related antimicrobial peptide. Through the following questions, we examine this paper in greater detail. For brief answers, please refer to the 〈supplementary information online〉 1.What is tacrolimus, and how does it work?2.What was the rationale for carrying out this study?3.How did the investigators perform their study, and what were their results?4.What were the conclusions and implications of the study? March 2011 Journal Club Answers and Discussion: Restoring Tacrolimus-Induced Impaired Barrier Function -- Answers Download .pdf (.07 MB) Help with pdf files Supplementary MaterialMarch 2011 Journal Club: Restoring Tacrolimus-Induced Impaired Barrier Function - Answers and Discussion" @default.
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• W2020093059 date "2011-03-01" @default.
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• W2020093059 title "Restoring Tacrolimus-Induced Impaired Barrier Function" @default.
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• W2020093059 doi "https://doi.org/10.1038/jid.2010.431" @default.
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