TGF-β1 Upregulates the Expression of Triggering Receptor Expressed on Myeloid Cells 1 in Murine Lungs.
TGF-β1 Upregulates the Expression of Triggering Receptor Expressed on Myeloid Cells 1 in Murine Lungs.
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DOI：
10.1038/srep18946
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发表时间：
2016-01-07
影响因子：
4.6
通讯作者：
Guan CX
中科院分区：
文献类型：
--
作者：
Peng L;Zhou Y;Dong L;Chen RQ;Sun GY;Liu T;Ran WZ;Fang X;Jiang JX;Guan CX
髓样细胞上表达的触发受体1（TREM-1）增加TGF-β家族基因的表达，其被称为肺纤维化发病机制中的促纤维化细胞因子。在这项研究中，我们确定TGF-β1是否调节肺纤维化小鼠模型中TREM-1的表达。BLM单次注射后第7、14、21天TGF-β1和TREM-1表达均增加。TGF-β1与TREM-1的表达呈正相关。TGF-β1以时间和剂量依赖性方式增加小鼠巨噬细胞TREM-1 mRNA和蛋白的表达。BLM注射后小鼠肺组织AP-1表达增强，TGF-β1处理后小鼠巨噬细胞AP-1表达增强。TGF-β1显著提高转染TREM-1野生型启动子的细胞荧光素酶的相对活性。但TGF-β1对转染了AP-1启动子结合位点突变的muglycer-TREM 1质粒的细胞中荧光素酶的活性没有影响。结论：肺纤维化小鼠肺组织中TREM-1表达增强。TGF-β1通过转录因子AP-1促进小鼠巨噬细胞TREM-1的表达。
Triggering receptor expressed on myeloid cells 1 (TREM-1) increases the expression of TGF-β family genes, which are known as profibrogenic cytokines in the pathogenesis of pulmonary fibrosis. In this study, we determined whether TGF-β1 regulated the expression of TREM-1 in a mouse model of pulmonary fibrosis. The expression of TGF-β1 and TREM-1 was increased on day 7, 14, and 21 after single intratracheal injection of bleomycin (BLM). And there was positive correlation between the expression of TGF-β1 and TREM-1. TGF-β1 increased expression of TREM-1 mRNA and protein in a time- and dose-dependent manner in mouse macrophages. The expression of the activator protein 1 (AP-1) was increased in lung tissues from mouse after BLM injection and in mouse macrophages after TGF-β1 treatment, respectively. TGF-β1 significantly increased the relative activity of luciferase in the cells transfected with plasmid contenting wild type-promoter of TREM-1. But TGF-β1 had no effect on the activity of luciferase in the cells transfected with a mutant-TREM1 plasmid carrying mutations in the AP-1 promoter binding site. In conclusion, we found the expression of TREM-1 was increased in lung tissues from mice with pulmonary fibrosis. TGF-β1 increased the expression of TREM-1 in mouse macrophages partly via the transcription factor AP-1.