Tacrolimus does alter the production of several cytokines and antimicrobial peptide in Malassezia furfur-infected-keratinocytes

Tacrolimus does alter the production of several cytokines and antimicrobial peptide in Malassezia furfur-infected-keratinocytes
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DOI:
10.1111/myc.12140
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发表时间:
2014-03-01
期刊:
影响因子:
4.9
通讯作者:
Donnarumma, Giovanna
Donnarumma, Giovanna
中科院分区:
医学2区
文献类型:
--
作者:
Balato, Anna;Paoletti, Iole;Donnarumma, Giovanna

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局部免疫抑制剂疗法广泛用于治疗炎症性皮肤病,例如特应性皮炎和牛皮癣。除了有益的治疗作用外,外用抗炎药物的应用还可能通过抑制角质形成细胞(KC)的先天免疫反应,使表皮更容易受到病原体的侵袭。上皮细胞产生的细胞因子、趋化因子和抗菌肽 (AMP) 使它们能够参与先天性和获得性免疫反应。本工作的目的是研究他克莫司(FK506)对糠秕马拉色菌(M.furfur)感染的KC的影响,评估促炎细胞因子IL-1和IL-6、趋化因子IL-8、抗炎细胞因子转化生长因子β1(TGF-1)和IL-10以及AMP-防御素-2的表达。人类 KC 是从正常成人皮肤的手术标本中获得的。通过实时定量聚合酶链反应对KC中mRNA的表达进行定量:FK506处理的、FK506处理的和糠秕马拉色菌感染的以及仅糠秕马拉色菌感染的。接下来,使用酶联免疫吸附测定评估AMP-防御素-2以及上述促炎和抗炎细胞因子的产生。在这项研究中,FK506 没有改变 KC 产生的细胞因子和 AMP;这使我们假设它可能不会增加真菌性皮肤感染的风险。
Topical immunosuppressant therapy is widely used in the treatment of inflammatory skin diseases, such as atopic dermatitis and psoriasis. Besides its beneficial therapeutic effects, application of topical anti-inflammatory drugs may render the epidermis more vulnerable to invading pathogens by suppressing innate immune responses in keratinocytes (KCs). Cytokines, chemokines and antimicrobial peptides (AMPs) produced by epithelial cells enable them to participate in innate and acquired immune responses. The aim of the present work was to study the influence of tacrolimus (FK506) on KCs infected with Malassezia furfur (M. furfur), evaluating the expression of pro-inflammatory cytokines IL-1 and IL-6, chemokine IL-8, anti-inflammatory cytokines transforming growth factor beta1 (TGF-1) and IL-10 and AMP -defensin-2. Human KCs were obtained from surgical specimens of normal adult skin. The expression of mRNAs in KCs: FK506-treated, FK506-treated and M. furfur-infected as well as only M. furfur-infected was quantified by real-time quantitative polymerase chain reaction. Next, the production of the AMP -defensin-2 and of the above-mentioned pro-inflammatory and anti-inflammatory cytokines was evaluated using enzyme-linked immunosorbent assay. In this study, FK506 did not alter cytokine and AMP production by KCs; this led us to hypothesise that it may not enhance the risk of mycotic skin infections.