Gene expression of inflammatory molecules in circulating lymphocytes from arsenic-exposed human subjects.
Gene expression of inflammatory molecules in circulating lymphocytes from arsenic-exposed human subjects.
复制标题
DOI：
10.1289/ehp.6396
复制
发表时间：
2003-08
影响因子：
10.4
通讯作者：
Lee TC
中科院分区：
文献类型：
--
作者：
Wu MM;Chiou HY;Ho IC;Chen CJ;Lee TC
长期接触砷会增加患血管疾病的风险，包括缺血性心脏病、脑血管疾病和颈动脉粥样硬化。砷致动脉粥样硬化的发病机制尚不完全清楚。炎症在动脉粥样硬化及其并发症中的基础作用最近已被认识到。为了探讨可能参与砷相关动脉粥样硬化的炎症途径的分子靶点，我们利用基因芯片和酶联免疫吸附试验进行了一项探索性研究，以寻找明显健康的砷暴露人群中差异表达的基因。作为初始实验，从24名低(0-4.32微克/L)、中(4.64-9.00微克/L)和高(9.60-46.5微克/L)血砷水平的研究对象的活化淋巴细胞中提取的基因进行阵列杂交，每组包括8名年龄、性别和吸烟频率匹配的个体。共分析了708个已知人类基因的转录本，其中62个转录本(8.8%)在中高砷组与低砷组之间存在显著差异。在显著改变的基因中，几种与炎症有关的细胞因子和生长因子，包括白介素1β、白介素6、趋化因子C-C基序配体2/单核细胞趋化蛋白1(CCL2/MCP1)、趋化因子C-X-C基序配体1/生长相关癌基因α、趋化因子C-X-C基序配体2/生长相关癌基因β、CD14抗原和基质金属蛋白酶1(间质胶原酶)在砷暴露增加的人群中表达上调。对不同砷暴露水平的研究对象进行的多因素分析显示，在调整了心血管疾病的其他危险因素后，CCL2/MCP1血浆蛋白水平与血砷的相关性仍然显著。这项基因表达研究结果显示，人体长期接触砷后，炎性分子的表达可能增加，这可能是台湾砷病病区动脉粥样硬化高危的原因之一。需要进一步的多学科研究，包括分子流行病学调查，以阐明砷相关炎症在动脉粥样硬化和随后的心血管疾病发展中的作用。
Long-term arsenic exposure is associated with an increased risk of vascular diseases including ischemic heart disease, cerebrovascular disease, and carotid atherosclerosis. The pathogenic mechanisms of arsenic atherogenicity are not completely clear. A fundamental role for inflammation in atherosclerosis and its complications has become appreciated recently. To investigate molecular targets of inflammatory pathway possibly involved in arsenic-associated atherosclerosis, we conducted an exploratory study using cDNA microarray and enzyme-linked immunosorbent assay to identify genes with differential expression in arsenic-exposed yet apparently healthy individuals. As an initial experiment, array hybridization was performed with mRNA isolated from activated lymphocytes of 24 study subjects with low (0-4.32 microg/L), intermediate (4.64-9.00 microg/L), and high (9.60-46.5 microg/L) levels of blood arsenic, with each group comprising eight age-, sex-, and smoking frequency-matched individuals. A total of 708 transcripts of known human genes were analyzed, and 62 transcripts (8.8%) showed significant differences in the intermediate or high-arsenic groups compared with the low-level arsenic group. Among the significantly altered genes, several cytokines and growth factors involving inflammation, including interleukin-1 beta, interleukin-6, chemokine C-C motif ligand 2/monocyte chemotactic protein-1 (CCL2/MCP1), chemokine C-X-C motif ligand 1/growth-related oncogene alpha, chemokine C-X-C motif ligand 2/growth-related oncogene beta, CD14 antigen, and matrix metalloproteinase 1 (interstitial collagenase) were upregulated in persons with increased arsenic exposure. Multivariate analyses on 64 study subjects of varying arsenic exposure levels showed that the association of CCL2/MCP1 plasma protein level with blood arsenic remained significant after adjustment for other risk factors of cardiovascular diseases. The results of this gene expression study indicate that the expression of inflammatory molecules may be increased in human subjects after prolonged exposure to arsenic, which might be a contributory factor to the high risk of atherosclerosis in arseniasis-endemic areas in Taiwan. Further multidisciplinary studies, including molecular epidemiologic investigations, are needed to elucidate the role of arsenic-associated inflammation in the development of atherosclerosis and subsequent cardiovascular disease.
登录
查看更多内容
影响因子：
5.3
作者：
Hsueh, YM;Wu, WL;Chen, CJ
通讯作者：
Chen, CJ
影响因子：
8.3
作者：
CHEN, CJ;HSUEH, YM;TAI, TY
通讯作者：
TAI, TY
影响因子：
10.4
作者：
Dong, ZG
通讯作者：
Dong, ZG
影响因子：
4.1
作者：
Chouchane, S;Snow, ET
通讯作者：
Snow, ET
影响因子：
11.4
作者：
Cavigelli, M;Li, WW;Karin, M
通讯作者：
Karin, M