Department of Dermatology, Tokyo Medical University, Tokyo, Japan.
Shiseido Life Science Research Center, Kanagawa, Japan.
J Dermatol. 2018 Aug;45(8):971-977. doi: 10.1111/1346-8138.14478. Epub 2018 May 24.
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.
炎症小体是一种多分子复合物，可控制炎症反应。炎症小体在银屑病发病机制中的作用尚不清楚。为了阐明炎症小体与银屑病病理生理学之间的关系，特别是鉴定与炎症小体关键成分半胱氨酸蛋白酶-1（caspase-1）相互作用的分子，我们用抗 caspase-1 抗体从银屑病患者的鳞屑中免疫沉淀，然后通过液相色谱-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症小体成分的表达。我们通过免疫沉淀和 LC-MS/MS 从银屑病鳞屑提取物中鉴定出几种 caspase-1 相互作用蛋白的候选物。核苷酸结合寡聚化结构域样受体家族 CARD 结构域蛋白 4（NLRC4）是候选物中唯一的炎症小体成分；因此，该蛋白被认为是银屑病炎症小体的关键因素。通过 LC-MS/MS 未在特应性皮炎或正常皮肤的提取物中发现炎症小体成分。免疫组织化学分析显示，一些银屑病患者皮损表皮中 NLRC4 上调，而正常和非皮损表皮中 NLRC4 表达较弱。在角质形成细胞融合后 48 小时，暴露于空气中后以及加入 1.5 mmol/L 氯化钙后，NLRC4 基因的 mRNA 表达增加。我们的研究结果表明，NLRC4 可能参与银屑病皮损的加重或改变。
