炎症体
表皮(动物学)
银屑病
免疫沉淀
免疫组织化学
发病机制
分子生物学
下调和上调
吡喃结构域
半胱氨酸蛋白酶1
化学
生物
细胞生物学
免疫学
炎症
抗体
生物化学
基因
解剖
作者
Junichiro Hiruma,Kazutoshi Harada,Akira Motoyama,Yukari Okubo,Tatsuo Maeda,Mami Yamamoto,Masashi Miyai,Toshihiko Hibino,Ryoji Tsuboi
标识
DOI:10.1111/1346-8138.14478
摘要
Abstract 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 ( NLRC 4) 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 NLRC 4 in the lesional epidermis of some psoriatic patients whereas weak expression of NLRC 4 was detected in the normal and non‐lesional epidermis. The mRNA expression of the NLRC 4 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 NLRC 4 may be involved in the exacerbation or modification of psoriatic lesions.
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