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血清骨膜蛋白水平:甲苯二异氰酸酯所致职业性哮喘的潜在血清学标志物

Serum Periostin Levels: A Potential Serologic Marker for Toluene Diisocyanate-Induced Occupational Asthma.

作者信息

Lee Ji Ho, Kim Sang Ha, Choi Youngwoo, Trinh Hoang Kim Tu, Yang Eun Mi, Ban Ga Young, Shin Yoo Seob, Ye Young Min, Izuhara Kenji, Park Hae Sim

机构信息

Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.

出版信息

Yonsei Med J. 2018 Dec;59(10):1214-1221. doi: 10.3349/ymj.2018.59.10.1214.

Abstract

PURPOSE

Toluene diisocyanate (TDI) is a leading cause of occupational asthma (OA). Periostin is a matricellular protein implicated in type 2 immunity-driven asthma. Its pathogenic role in TDI-OA has not been completely elucidated. The present study was performed to investigate the role of periostin in TDI-OA.

MATERIALS AND METHODS

Serum periostin levels were measured in subjects with TDI-OA, asymptomatic TDI-exposure controls (AECs), non-occupational asthmatics (NAs), and unexposed normal controls (NCs). To understand the mechanism by which TDI induces periostin production, primary small airway epithelial cells (SAECs) were cultured under stimulation of TDI and neutrophils from asthmatic patients.

RESULTS

Fifty-three subjects with TDI-OA, 71 AECs, 67 NAs, and 83 NCs were enrolled. Serum periostin levels were significantly higher in TDI-OA subjects than in AECs (=0.001), NAs (<0.001), and NCs (<0.001). In TDI-exposed subjects (TDI-OA and AEC), the PC₂₀ methacholine levels were significantly lower in subjects with a higher periostin level than in those with a lower periostin level. TDI exposure did not increase periostin production directly by SAECs; however, periostin production increased significantly after co-culture with TDI and neutrophils, which was suppressed by an antioxidant. In addition, increased release of TGF-β1 was noted from SAECs when exposed to TDI and neutrophils, which was also suppressed by an antioxidant.

CONCLUSION

These results suggest that an increased periostin level may contribute to the progression of airway inflammation to remodeling in TDI-exposed workers. A high serum periostin level is a potential serologic marker of the phenotype of TDI-OA.

摘要

目的

甲苯二异氰酸酯(TDI)是职业性哮喘(OA)的主要病因。骨膜蛋白是一种基质细胞蛋白,与2型免疫驱动的哮喘有关。其在TDI-OA中的致病作用尚未完全阐明。本研究旨在探讨骨膜蛋白在TDI-OA中的作用。

材料与方法

检测TDI-OA患者、无症状TDI暴露对照者(AECs)、非职业性哮喘患者(NAs)和未暴露正常对照者(NCs)的血清骨膜蛋白水平。为了解TDI诱导骨膜蛋白产生的机制,在TDI和哮喘患者中性粒细胞的刺激下培养原代小气道上皮细胞(SAECs)。

结果

纳入53例TDI-OA患者、71例AECs、67例NAs和83例NCs。TDI-OA患者的血清骨膜蛋白水平显著高于AECs(P = 0.001)、NAs(P < 0.001)和NCs(P < 0.001)。在TDI暴露的受试者(TDI-OA和AEC)中,骨膜蛋白水平较高的受试者的乙酰甲胆碱激发浓度(PC₂₀)显著低于骨膜蛋白水平较低的受试者。TDI暴露不会直接增加SAECs产生骨膜蛋白;然而,与TDI和中性粒细胞共培养后,骨膜蛋白的产生显著增加,而抗氧化剂可抑制这种增加。此外,当SAECs暴露于TDI和中性粒细胞时,观察到转化生长因子-β1(TGF-β1)的释放增加,抗氧化剂也可抑制这种增加。

结论

这些结果表明,骨膜蛋白水平升高可能有助于TDI暴露工人气道炎症向重塑的进展。高血清骨膜蛋白水平是TDI-OA表型的潜在血清学标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea0/6240562/34759917a2ad/ymj-59-1214-g001.jpg

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