Isshiki Takuma, Sunakawa Motoko, Vierhout Megan, Ayoub Anmar, Ali Pareesa, Naiel Safaa, Miyoshi Shion, Naqvi Asghar, Hambly Nathan, Kishi Kazuma, Ask Kjetil, Kolb Martin R J
Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, Canada.
Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, ON, Canada.
Front Med (Lausanne). 2025 Jan 15;12:1532437. doi: 10.3389/fmed.2025.1532437. eCollection 2025.
Sarcoidosis is a systemic granulomatous disease of unknown cause. Natural improvement with favorable outcome is common, but a significant number of patients present with difficult to manage and progressive disease. The identification of biomarkers associated with disease activity and progression is warranted. Extracellular heat shock protein 90 (HSP90) is a signaling molecule released by cells that induces proinflammatory signaling through interaction with certain receptors, such as lipoprotein receptor-related protein 1.
HSP90α protein expression in lung tissues derived from patients diagnosed with sarcoidosis and control subjects was assessed by immunohistochemistry. Serum HSP90α concentration was measured in sarcoidosis patients and healthy controls and correlated with clinical outcomes. Bronchoalveolar lavage fluid (BALF) was collected and analyzed for HSP90α expression. Extracellular HSP90α released from macrophages was examined in human primary cells and an immortalized cell line.
Macrophages and granulomas in sarcoidosis-affected lungs showed high HSP90α expression. Serum HSP90α levels were elevated in sarcoidosis patients compared with controls and correlated with BALF HSP90α levels. HSP90α concentrations in the circulation were correlated with biomarkers of disease stage. Both primary and immortalized macrophages showed a high capacity for secreting extracellular HSP90α.
These results demonstrate that macrophages in the lungs of sarcoidosis patients produce high levels of HSP90α, suggesting HSP90α as a potential biomarker and therapeutic target.
结节病是一种病因不明的全身性肉芽肿性疾病。自然改善且预后良好的情况很常见，但仍有相当数量的患者表现为难以控制的进行性疾病。因此，有必要识别与疾病活动和进展相关的生物标志物。细胞外热休克蛋白90（HSP90）是细胞释放的一种信号分子，它通过与某些受体（如脂蛋白受体相关蛋白1）相互作用诱导促炎信号传导。
通过免疫组织化学评估结节病患者和对照受试者肺组织中HSP90α蛋白的表达。测定结节病患者和健康对照者血清中HSP90α的浓度，并将其与临床结果相关联。收集支气管肺泡灌洗液（BALF）并分析其中HSP90α的表达。在原代人细胞和永生化细胞系中检测巨噬细胞释放的细胞外HSP90α。
结节病患者肺部的巨噬细胞和肉芽肿显示出高HSP90α表达。与对照组相比，结节病患者血清HSP90α水平升高，且与BALF中HSP90α水平相关。循环中HSP90α的浓度与疾病分期的生物标志物相关。原代巨噬细胞和永生化巨噬细胞均显示出分泌细胞外HSP90α的高能力。
这些结果表明，结节病患者肺部的巨噬细胞产生高水平的HSP90α，提示HSP90α作为一种潜在的生物标志物和治疗靶点。
