摘要
目的探讨DnaJA4对咪喹莫特诱导小鼠银屑病样皮肤炎症的影响。方法4组小鼠(每组8只),即应用咪喹莫特(imiquimod,IMQ)诱导银屑病样皮炎的DnaJA4敲除(knockout,KO-IMQ)组小鼠及野生型(wild-type,WT-IMQ)小鼠,涂以等量凡士林的DnaJA4敲除(knockout,KO-blank)组小鼠及野生型(wild-type,WT-blank)小鼠。银屑病皮损面积及严重程度指数(psoriasis area and severity index,PASI)评价IMQ诱导的小鼠银屑病样皮损表现。HE染色观察皮损病理特征。免疫组织化学染色观察小鼠皮损表皮IL-6、IL-17、IL-27、C-X-C型趋化因子配体1(C-X-C motif ligand 1,CXCL1)阳性程度及银屑病患者与正常对照皮肤组织内DnaJA4表达情况。结果IMQ诱导的银屑病样皮炎小鼠模型中,DnaJA4-KO小鼠出现更严重的红斑,皮肤增厚更明显,累积PASI评分在第3~5天明显高于WT小鼠,并较WT小鼠真皮更早出现炎症细胞,浸润细胞数更多,且在应用IMQ的第4天见更大面积的Munro's微脓肿。IMQ诱导的DnaJA4-KO小鼠银屑病样皮损表皮内IL-6、IL-17、CXCL1均较WT小鼠呈上调表达;DnaJA4未见于银屑病患者皮损组织,但在正常皮肤组织表皮基底细胞阳性表达。结论DnaJA4敲除通过上调表皮内促炎细胞因子及趋化因子表达加重IMQ诱导的小鼠银屑病样皮肤炎症,并影响Munro's微脓肿形成。
Objective To investigate the effect of DnaJA4 on imiquimod-induced psoriasis-like skin inflammation in mice.Methods All mice were divided into 4 groups(8 mice in one group),namely DnaJA4-KO mice and WT mice treated with IMQ on back,and DnaJA4-KO mice and WT mice applied with equal amount of Vaseline.PASI score system was uesd to evaluate the manifestation of IMQ-induced psoriasis-like lesions.HE staining was used to observe the pathological features.IHC staining was performed to observe the expression of IL-6,IL-17,IL-27,CXCL1 and DnaJA4.Results IMQ-treated DnaJA4-KO mice had more severe erythema and thicker skin.The cumulative PASI score was significantly higher than that of WT mice on day 3~5.More inflammatory cells infiltrated in the dermis earlier in DnaJA4-KO mice.IMQ-induced DnaJA4-KO mice showed a larger area of Munro's microabscess on the Day 4.Immunohistochemically showed that the epression of IL-6,IL-17,and CXCL1 in psoriasis-like lesions in epidermal of DnaJA4-KO mice were up-regulated compared with WT mice.DnaJA4 was positive expressed in basal cells of normal skin,but not in psoriatic lesions.Conclusion DnaJA4 knockout could aggravate IMQ-induced psoriasis-like skin inflammation in mice by up-regulating the expression of pro-inflammatory cytokines and chemokines in the epidermis,moreover,affect the formation of Munro's microabscess.
作者
吴泽
牛雪丽
陈佳龙
刘瑞姣
马蕾
高兴华
陈洪铎
齐瑞群
WU Ze;NIU Xueli;CHEN Jialong;LIU Ruijiao;MA Lei;GAO Xinghua;CHEN Hongduo;QI Ruiqun(The First Hospital of China Medical University,NHC Key Laboratory of Immunodermatology,China Medical University,Shenyang 110001,China;Department of Dermatology,Binzhou Medical University Hospital,Binzhou 256603,China)
出处
《中国皮肤性病学杂志》
CAS
CSCD
北大核心
2021年第8期841-848,共8页
The Chinese Journal of Dermatovenereology
基金
国家自然科学基金资助项目(81673070,81872538)。
