Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients
Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients
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DOI：
10.1111/1346-8138.14478
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发表时间：
2018-08-01
影响因子：
3.1
通讯作者：
Tsuboi, Ryoji
中科院分区：
文献类型：
--
作者：
Hiruma, Junichiro;Harada, Kazutoshi;Tsuboi, Ryoji
炎性小体是控制炎症反应的多分子复合物。炎性小体在银屑病发病机制中的作用尚不清楚。为了阐明炎性小体与银屑病病理生理学之间的关系，特别是为了鉴定与炎性小体的关键组分caspase-1相互作用的分子，用抗caspase-1抗体免疫沉淀从银屑病患者获得的鳞片提取物，并通过液相色谱-电喷雾串联质谱（LC-MS/MS）进行分析。通过免疫组织化学分析和体外测定评估炎性体组分的表达。我们通过免疫沉淀和LC-MS/MS从银屑病鳞屑提取物中鉴定了几种与caspase-1相互作用的候选蛋白。核苷酸结合寡聚化结构域含蛋白样受体家族CARD结构域含蛋白4（NLRC 4）是候选蛋白中唯一的炎性小体组分;因此，该蛋白被认为是银屑病炎性小体的关键因子。LC-MS/MS法在特应性皮炎或正常皮肤的提取物中未发现炎性小体成分。免疫组化分析表明，在一些银屑病患者的皮损表皮中NLRC 4表达上调，而在正常和非皮损表皮中检测到NLRC 4的弱表达。角质形成细胞在汇合时、空气暴露后48 h和加入1.5 mmol/L氯化钙后NLRC 4基因的mRNA表达增加。我们的研究结果表明，NLRC 4可能参与银屑病病变的加重或修饰。
Inflammasomes are multimolecular complexes that control the inflammatory response. The function of inflammasomes in the pathogenesis of psoriasis is still unclear. To clarify the relationship between inflammasomes and the pathophysiology of psoriasis, and in particular, to identify molecules interacting with caspase-1, a crucial component of inflammasomes, scale extracts obtained from patients with psoriasis were immunoprecipitated with anti-caspase-1 antibody and analyzed by liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS). The expression of the inflammasome component was assessed by immunohistochemical analysis and an in vitro assay. We identified several candidates for caspase-1-interacting proteins from the psoriatic scale extracts by immunoprecipitation and LC-MS/MS. Nucleotide-binding oligomerization domain-containing protein-like receptor family CARD domain-containing protein 4 (NLRC4) was the only inflammasome component among the candidates; thus, the protein is considered to be a key factor of inflammasomes in psoriasis. No inflammasome component was found in the extracts of atopic dermatitis or normal skin by LC-MS/MS. Immunohistochemical analysis demonstrated upregulation of NLRC4 in the lesional epidermis of some psoriatic patients whereas weak expression of NLRC4 was detected in the normal and non-lesional epidermis. The mRNA expression of the NLRC4 gene increased in keratinocytes at confluency, 48 h after air exposure and after the addition of 1.5 mmol/L calcium chloride. Our findings suggest that NLRC4 may be involved in the exacerbation or modification of psoriatic lesions.