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NLRP3 炎性小体在系统性和皮肤性红斑狼疮患者皮肤中的激活。

Activation of NLRP3 Inflammasome in the Skin of Patients with Systemic and Cutaneous Lupus Erythematosus.

机构信息

Department of Dermatology and Allergology, Skin and Allergy Hospital, P.O. Box 160, FIN-00029 Helsinki, Finland.

出版信息

Acta Derm Venereol. 2022 May 10;102:adv00708. doi: 10.2340/actadv.v102.2293.

DOI:10.2340/actadv.v102.2293
PMID:35356994
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9593479/
Abstract

NLRP3 inflammasome is suggested to contribute to the complex pathogenesis of systemic lupus erythematosus, but its role in cutaneous lupus erythematosus has not been addressed. This study investigated the expression of NLRP3 inflammasome components and levels of type I interferons in the skin of 20 patients with cutaneous lupus erythematosus. Expression of NLRP1/3, adaptor protein ASC (apoptosis-associated speck-like protein), caspase-1, interferon-α (IFN-α), myxovirus resistance protein (MxA), and interferon-induced proteins 1 and 2 (IFIT 1/2) in the skin was assessed using reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and immunohistochemistry. Serum interferon-α protein levels from 12 patients were measured using digital enzyme-linked immunoassay (ELISA). Interleukin-1β expression was significantly upregulated in the lesional skin of patients with cutaneous lupus erythematosus compared with their uninvolved skin. However, NLRP1/3, ASC and caspase-1 were not significantly upregulated compared with the skin of control persons. IFN-α and IFN-induced proteins MxA and IFIT1/2 were strongly expressed in cutaneous lupus erythematosus skin. Variability in the expression of NLRP3 inflammasome components among patients suggests heterogeneity of pathological pathways in cutaneous lupus erythematosus.

摘要

NLRP3 炎性体被认为有助于全身性红斑狼疮的复杂发病机制,但它在皮肤性红斑狼疮中的作用尚未得到解决。本研究调查了 20 例皮肤性红斑狼疮患者皮肤中 NLRP3 炎性体成分的表达和 I 型干扰素的水平。使用逆转录定量实时 PCR(RT-qPCR)、western 印迹和免疫组织化学法评估 NLRP1/3、衔接蛋白 ASC(凋亡相关斑点样蛋白)、半胱天冬酶-1、干扰素-α(IFN-α)、抗黏液病毒蛋白(MxA)和干扰素诱导蛋白 1 和 2(IFIT1/2)在皮肤中的表达。使用数字酶联免疫吸附测定(ELISA)测量 12 例患者的血清干扰素-α蛋白水平。与未受累皮肤相比,皮肤性红斑狼疮患者皮损皮肤中白细胞介素-1β的表达显著上调。然而,与对照组皮肤相比,NLRP1/3、ASC 和半胱天冬酶-1的表达没有显著上调。IFN-α和 IFN 诱导的 MxA 和 IFIT1/2 蛋白在皮肤性红斑狼疮皮肤中强烈表达。患者 NLRP3 炎性体成分表达的可变性表明皮肤性红斑狼疮中病理途径的异质性。

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