Induction of IL-1β and antimicrobial peptides as a potential mechanism for topical dithranol.
Induction of IL-1β and antimicrobial peptides as a potential mechanism for topical dithranol.
复制标题
诱导IL-1β和抗菌肽作为外用双乙醇的潜在机制。
DOI：
10.1111/exd.14310
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发表时间：
2021-06
影响因子：
3.6
通讯作者：
Wolf P
中科院分区：
文献类型：
--
作者：
Benezeder T;Gehad A;Patra V;Clark R;Wolf P
局部地蒽酚对斑秃等自身免疫性疾病有效，在很高比例的病例中诱导毛发再生。地蒽酚治疗斑秃的确切机制还不清楚，斑秃除了毛囊改变外，表皮似乎很健康。为了更好地了解地蒽酚对健康皮肤的作用机制，我们分析了它对正常小鼠和异种移植的人类皮肤的作用。我们发现健康小鼠皮肤中抗菌肽（AMP）（例如Lcn 2、Defb 1、Defb 3、S100 a8、S100 a9）、角质形成细胞分化标志物（例如Serpinb 3a、Flg、Krt 16、Lce 3e）和炎性细胞因子（例如Il 1b和Il 17）的mRNA表达显著增加。这种作用被炎症和扰乱的皮肤屏障以及导致表皮过度增殖的损伤反应所抵消，如在小鼠和异种移植的成人皮肤中所观察到的。这种由地蒽酚诱导的接触反应和屏障紊乱可能通过AMP如S100 a8/a9（局部应用后导致皮肤肿胀）和细胞因子如IL-1β之间的恶性循环导致皮肤中的免疫抑制环境。更好地了解皮肤对地蒽酚的生理反应可能会为某些皮肤疾病（如斑秃）的新型治疗方法（包括AMP相关/干扰分子）的建立开辟新的途径。
Topical dithranol is effective in autoimmune conditions like alopecia areata, inducing hair regrowth in a high percentage of cases. Exact mechanisms of dithranol in alopecia areata, with seemingly healthy epidermis besides altered hair follicles, are not well understood. To better understand dithranol's mechanisms on healthy skin, we analysed its effect on normal murine as well as xenografted human skin. We found a strong increase in mRNA expression of anti‐microbial peptides (AMPs) (eg Lcn2, Defb1, Defb3, S100a8, S100a9), keratinocyte differentiation markers (eg Serpinb3a, Flg, Krt16, Lce3e) and inflammatory cytokines (eg Il1b and Il17) in healthy murine skin. This effect was paralleled by inflammation and disturbed skin barrier, as well as an injury response resulting in epidermal hyperproliferation, as observed in murine and xenografted adult human skin. This contact response and disturbed barrier induced by dithranol might lead via a vicious loop between AMPs such as S100a8/a9 (that led to skin swelling itself after topical application) and cytokines such as IL‐1β to an immune suppressive environment in the skin. A better understanding of the skin's physiologic response to dithranol may open up new avenues for the establishment of novel therapeutics (including AMP‐related/interfering molecules) for certain skin conditions, such as alopecia areata.
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影响因子：
6.5
作者：
Kennedy-Crispin, Milene;Billick, Erika;Mitsui, Hiroshi;Gulati, Nicholas;Fujita, Hideki;Gilleaudeau, Patricia;Sullivan-Whalen, Mary;Johnson-Huang, Leanne M.;Suarez-Farinas, Mayte;Krueger, James G.
通讯作者：
Krueger, James G.
IL-1β-IL-1R信号通路在皮肤炎症和牛皮癣发病机理中的关键作用。
DOI：
10.1016/j.jid.2018.07.025
发表时间：
2019-01
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Cai Y;Xue F;Quan C;Qu M;Liu N;Zhang Y;Fleming C;Hu X;Zhang HG;Weichselbaum R;Fu YX;Tieri D;Rouchka EC;Zheng J;Yan J
通讯作者：
Yan J
影响因子：
6.5
作者：
Liu, AY;Destoumieux, D;Ganz, T
通讯作者：
Ganz, T
影响因子：
6.5
作者：
Hoffmann, R;Eicheler, W;Happle, R
通讯作者：
Happle, R
影响因子：
15.9
作者：
KUPPER, TS;CHUA, AO;GUBLER, U
通讯作者：
GUBLER, U