Inhibited proliferation of human lung fibroblasts by LPS is through IL-6 and IL-8 release.
Inhibited proliferation of human lung fibroblasts by LPS is through IL-6 and IL-8 release.
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DOI：
10.1016/j.cyto.2011.02.018
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发表时间：
2011-06
期刊：
影响因子：
3.8
通讯作者：
Jing Zhang;Lian Wu;J. Qu
中科院分区：
文献类型：
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作者：
Jing Zhang;Lian Wu;J. Qu
通过对慢性阻塞性肺疾病（COPD）患者肺成纤维细胞增殖能力下降及脂多糖（LPS）在COPD发病中的促炎作用的研究，我们推测LPS可能抑制肺成纤维细胞增殖，并探讨其可能机制。从外周肺组织培养原代人肺成纤维细胞，然后用或不用LPS处理。通过AlamarBlue®测定测量增殖。ELISA法检测培养上清中TNF-α、IL-6、IL-8、IL-12 p70、IL-1β和IL-10的水平。采用实时荧光定量PCR分析组蛋白去乙酰化酶2（HDAC 2）的mRNA。LPS对成纤维细胞增殖有剂量依赖性抑制作用。处理培养基中IL-6和IL-8的浓度显著增加，伴随着HDAC 2的mRNA表达减少。IL-6或IL-8本身导致成纤维细胞增殖减少。在成纤维细胞中用1 ng/ml TNF-α处理也引起增殖显著降低和IL-8和IL-6的产生增加。我们的数据表明，LPS可以抑制体外人肺成纤维细胞的增殖，至少通过产生IL-6和IL-8。细胞因子应答与HDAC 2转录降低有关。
Through the consideration of decreased proliferation of lung fibroblasts from subjects with chronic obstructive pulmonary disease (COPD) and the proinflammatory role of lipopolysaccharide (LPS) in the COPD development, we hypothesized that LPS might inhibit proliferation in lung fibroblasts and the possible mechanism was investigated. Primary human lung fibroblasts were cultured from peripheral lung tissue and then treated with or without LPS. Proliferation was measured by AlamarBlue® assay. Levels of TNF-α, IL-6, IL-8, IL-12p70, IL-1β and IL-10 in the supernatants were measured by ELISA. The mRNA of histone deacetylases 2 (HDAC2) was analyzed using real-time PCR. LPS appeared to have a dose-dependent inhibitory effect on fibroblasts proliferation. The concentrations of IL-6 and IL-8 in the treatment culture media were significantly increased, accompanied by a reduced mRNA expression of HDAC2. IL-6 or IL-8 itself led to the reduction of fibroblasts proliferation. Treatment with 1ng/ml TNF-α in fibroblasts also caused a significant decrease in proliferation and an increase in the production of IL-8 and IL-6. Our data suggest that LPS can inhibit the proliferation of in vitro human lung fibroblasts at least through a production of IL-6 and IL-8. The cytokine response is related to the decreased HDAC2 transcription.