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基因多态性对煤工尘肺患者肿瘤坏死因子α和白细胞介素1细胞因子释放的可能影响。

Possible effect of gene polymorphisms on the release of TNFα and IL1 cytokines in coal workers' pneumoconiosis.

作者信息

Ates Ilker, Yucesoy Berran, Yucel Aysegul, Suzen Sinan H, Karakas Yalcin, Karakaya Asuman

机构信息

Department of Toxicology, Faculty of Pharmacy, Ankara University, Tandogan, Ankara 06100, Turkey.

出版信息

Exp Toxicol Pathol. 2011 Jan;63(1-2):175-9. doi: 10.1016/j.etp.2009.11.006. Epub 2009 Dec 11.

DOI:10.1016/j.etp.2009.11.006
PMID:20005085
Abstract

It has been shown that coal dust exposure stimulates inflammatory response leading to increased release of cytokines from monocytes such as TNF-alpha and IL1. These released cytokines play the key role in the pathogenesis of pneumoconiosis including coal workers' pneumoconiosis. In this study, we investigated TNFA, IL1A, IL1B and IL1RA genes variations on basal, lipopolysaccharide and coal dust-induced cytokine release from blood monocytes of homozygous allele and minor variant allele carriers in Turkish coal workers and CWP patients. According to the genotyping results, TNFA -238 gene polymorphism was found as a risk factor in CWP development (OR=3.79) and to in vitro results; release of both TNF-alpha and IL1 cytokines from the monocytes in CWP patients was significantly increased compared to the healthy workers. Also, LPS and coal dust stimulated release of TNF-alpha, which was significantly higher in allele 2 carriers compared to subjects carrying allele 1 in both the groups. These data suggest that the coal dust-induced release of TNF-alpha from monocytes may be a useful biomarker of CWP.

摘要

研究表明,接触煤尘会刺激炎症反应,导致单核细胞释放更多细胞因子,如肿瘤坏死因子-α(TNF-α)和白细胞介素-1(IL1)。这些释放的细胞因子在尘肺病(包括煤工尘肺)的发病机制中起关键作用。在本研究中,我们调查了土耳其煤工和煤工尘肺患者中纯合等位基因和次要变异等位基因携带者的血液单核细胞在基础状态、脂多糖和煤尘诱导下,肿瘤坏死因子-α(TNFA)、白细胞介素-1α(IL1A)、白细胞介素-1β(IL1B)和白细胞介素-1受体拮抗剂(IL1RA)基因变异对细胞因子释放的影响。根据基因分型结果,发现TNFA -238基因多态性是煤工尘肺发展的一个危险因素(比值比=3.79),并且与体外实验结果一致;与健康工人相比,煤工尘肺患者单核细胞中TNF-α和IL1细胞因子的释放显著增加。此外,脂多糖和煤尘刺激TNF-α的释放,在两组中,携带等位基因2的个体相比携带等位基因1的个体,TNF-α的释放显著更高。这些数据表明,煤尘诱导单核细胞释放TNF-α可能是煤工尘肺的一个有用生物标志物。

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