Hu Feng, Qu Zilu, Chen Kai, Zhang Ping, Wang Bei, Jiang Ruili, Zuo Yuyue, Xia Ping, Chen Hongxiang
Department of Dermatology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Hubei Province & Key Laboratory of Skin Infection and Immunity, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Clin Cosmet Investig Dermatol. 2023 Aug 8;16:2103-2111. doi: 10.2147/CCID.S418467. eCollection 2023.
As a mediator of inflammation resolution, lipoxin A4 (LXA4) mainly plays an anti-inflammatory role and promotes inflammation resolution. LXA4 plays an inhibiting inflammatory role in a variety of diseases, tissues and cells, including keratinocytes. Psoriasis is a chronic inflammatory skin disease mediated by dysregulation of inflammation of immune cells and keratinocytes. However, the expression and role of LXA4 in psoriasis-like mouse models are still unclear.
Imiquimod (IMQ) topical treatment of dorsal skin induces psoriasis-like dermatitis in BALB/c mice, pretreated intraperitoneally with or without LXA4 prior to IMQ application. Severity of dorsal lesions is assessed by using a modified human scoring system and histopathology. The concentration of LXA4 and the expression of ALOX15 (a key gene in LXA4 metabolic synthesis) in lesional skins were detected by ELISA and Western blot. Quantitative PCR and ELISA were conducted to detect the mRNA and secretion levels of inflammatory cytokines. The proportion of IL-17A-producing γδT cells in skin and skin draining cervical lymph nodes and helper (Th) 17 cells in spleens was evaluated by flow cytometry. Western blotting was used to analyze the expressions of p-STAT3 and TRAF6.
The concentration of LXA4 and the expression of ALOX15 were decreased in IMQ-induced lesional skin. LXA4 significantly relieved psoriasis-like lesions in IMQ-induced mouse models. Furthermore, LXA4 decreased IMQ-induced systemic inflammation, including reduced the proportion of IL-17A-producing gdT cells in skin and skin draining cervical lymph nodes and Th17 cells in spleens, the secretion and expression of CCL20, IL-17A, IL-1β, and TNF-α in skin and serum. LXA4 markedly inhibited IMQ-induced expression of TRAF6 and p-STAT3.
LXA4 significantly ameliorates IMQ-induced psoriasis-like inflammation, and LXA4 can be used as a target for psoriasis treatment.
作为炎症消退的介质，脂氧素A4（LXA4）主要发挥抗炎作用并促进炎症消退。LXA4在多种疾病、组织和细胞（包括角质形成细胞）中发挥抑制炎症的作用。银屑病是一种由免疫细胞和角质形成细胞炎症失调介导的慢性炎症性皮肤病。然而，LXA4在银屑病样小鼠模型中的表达和作用仍不清楚。
用咪喹莫特（IMQ）局部处理背部皮肤可在BALB/c小鼠中诱导银屑病样皮炎，在应用IMQ之前，对小鼠进行腹腔注射LXA4预处理或不进行预处理。使用改良的人类评分系统和组织病理学评估背部病变的严重程度。通过酶联免疫吸附测定（ELISA）和蛋白质印迹法检测病变皮肤中LXA4的浓度和15-脂氧合酶（ALOX15，LXA4代谢合成中的关键基因）的表达。进行定量聚合酶链反应（PCR）和ELISA以检测炎性细胞因子的信使核糖核酸（mRNA）和分泌水平。通过流式细胞术评估皮肤和引流颈部皮肤淋巴结中产生白细胞介素-17A（IL-17A）的γδT细胞以及脾脏中辅助性（Th）17细胞的比例。用蛋白质印迹法分析磷酸化信号转导子和转录激活子3（p-STAT3）和肿瘤坏死因子受体相关因子6（TRAF6）的表达。
在IMQ诱导的病变皮肤中，LXA4的浓度和ALOX15的表达降低。LXA4显著减轻了IMQ诱导的小鼠模型中的银屑病样病变。此外，LXA4减轻了IMQ诱导的全身炎症，包括降低了皮肤和引流颈部皮肤淋巴结中产生IL-17A的γδT细胞以及脾脏中Th17细胞的比例，皮肤和血清中趋化因子配体20（CCL20）、IL-17A、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的分泌和表达。LXA4显著抑制了IMQ诱导的TRAF6和p-STAT3的表达。
LXA4显著改善IMQ诱导的银屑病样炎症，LXA4可作为银屑病治疗的靶点。
