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在意大利沿海地区有胸膜恶性间皮瘤地域聚集的石棉暴露工人中,参与早期炎症反应和促肿瘤活性的趋化因子。

Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma.

作者信息

Comar M, Zanotta N, Zanconati F, Cortale M, Bonotti A, Cristaudo A, Bovenzi M

机构信息

Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy; Clinical Unit of Hygiene, Department of Medical Sciences, University of Trieste, Trieste, Italy.

Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.

出版信息

Lung Cancer. 2016 Apr;94:61-7. doi: 10.1016/j.lungcan.2016.01.020. Epub 2016 Feb 1.

DOI:10.1016/j.lungcan.2016.01.020
PMID:26973208
Abstract

OBJECTIVES

Immune mediators are likely to be relevant for the biological response to asbestos exposure. The aim of this study was to investigate the association between immune mediators involved in inflammation, cell survival and angiogenesis, and asbestos-related diseases in workers from a coastal area of North-East Italy with a high incidence of pleural malignant mesothelioma (PMM).

MATERIALS AND METHODS

A selected custom set of 12 soluble mediators was evaluated with a Luminex platform in sera, pleural fluid and mesothelioma biopsies from 123 asbestos-exposed workers (38 free from pleural-pulmonary disorders, 46 with non-malignant asbestos diseases, 39 with PMM) and in sera from 33 healthy controls from the same territorial area.

RESULTS

Increased immune mediator concentrations were observed in the sera of the asbestos-exposed workers compared to controls for human fibroblast growth factor (FGF-b), vascular endothelial growth factor (VEGF), CCL5 (RANTES), CXCL10 (IP-10), CLEC11A (SCGF-b), CCL27 (CTACK), CCL11 (EOTAXIN), IL-5 and IL-6 (p<0.001). The chemokines IP-10 and RANTES were associated with the severity of asbestos-related diseases. In the workers with PMM, the immune proteins secreted by mesothelioma biopsies showed detectable levels of RANTES, VEGF, and IP-10. In the same workers with PMM, a significant relationship between serum and pleural fluid concentrations was found for RANTES alone.

CONCLUSIONS

Occupational exposure to asbestos seems to drive the production of specific growth factors dually involved in the early inflammatory response and in pro-tumoral activity before clinical evidence of related disorders, suggesting that their over-expression may precede the onset of asbestos-related diseases. These findings suggest that some chemokines may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by non-malignant asbestos-related diseases.

摘要

目的

免疫介质可能与石棉暴露的生物学反应相关。本研究旨在调查参与炎症、细胞存活和血管生成的免疫介质与意大利东北部沿海地区胸膜恶性间皮瘤(PMM)发病率较高的工人中石棉相关疾病之间的关联。

材料与方法

使用Luminex平台评估了一组选定的12种可溶性介质,这些介质来自123名接触石棉的工人(38名无胸膜肺部疾病、46名患有非恶性石棉疾病、39名患有PMM)的血清、胸水和间皮瘤活检组织,以及来自同一地区的33名健康对照者的血清。

结果

与对照组相比,接触石棉的工人血清中人类成纤维细胞生长因子(FGF-b)、血管内皮生长因子(VEGF)、CCL5(RANTES)、CXCL10(IP-10)、CLEC11A(SCGF-b)、CCL27(CTACK)、CCL11(嗜酸性粒细胞趋化因子)、IL-5和IL-6的免疫介质浓度升高(p<0.001)。趋化因子IP-10和RANTES与石棉相关疾病的严重程度相关。在患有PMM的工人中,间皮瘤活检组织分泌的免疫蛋白显示出可检测水平的RANTES、VEGF和IP-10。在同一组患有PMM的工人中,仅发现RANTES的血清和胸水浓度之间存在显著关系。

结论

职业性接触石棉似乎会促使特定生长因子的产生,这些生长因子在相关疾病的临床证据出现之前,就双重参与早期炎症反应和促肿瘤活性,这表明它们的过度表达可能先于石棉相关疾病的发生。这些发现表明,一些趋化因子可能在石棉相关疾病的进展中具有预后作用,可用于对有石棉接触职业史的工人或患有非恶性石棉相关疾病的患者进行健康监测。

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