TREM-1 expression in macrophages is regulated at transcriptional level by NF-κB and PU.1
TREM-1 expression in macrophages is regulated at transcriptional level by NF-κB and PU.1
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DOI：
10.1002/eji.200737270
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发表时间：
2007-08-01
影响因子：
5.4
通讯作者：
Sadikot, Ruxana T.
中科院分区：
文献类型：
--
作者：
Zeng, Heng;Ornatowska, Magdalena;Sadikot, Ruxana T.
骨髓细胞上表达的触发受体 (TREM)-1 是最近发现的一种免疫球蛋白受体，它在中性粒细胞和单核细胞上表达，可放大对细菌的急性炎症反应。我们检查了巨噬细胞中 TREM-1 的转录调控。用大肠杆菌 LPS 或铜绿假单胞菌处理 RAW 细胞，可在 1 小时内诱导 TREM-1，并且通过 RT-PCR 检测，其表达在体外持续至少 24 小时。由于 TREM-1 的启动子具有多个 NF-kappa B 和 PU.1（转录因子 ets 家族成员之一）的结合位点，因此我们研究了这些转录因子在 TREM-1 诱导中的作用。用 NF-κ B 抑制剂处理细胞消除了 LPS 和铜绿假单胞菌诱导的 TREM-1 信息表达。相反，在PU.1基因沉默的细胞中，用LPS或铜绿假单胞菌刺激后，TREM-1的表达增加。此外，PU.1 的过度表达导致对 LPS 和铜绿假单胞菌响应的 TREM-1 诱导受到抑制。这些数据表明这两种转录因子均参与 TREM-1 的表达。 NF-kappa B 充当正调节因子，而 PU.1 是 TREM-1 基因的负调节因子。
Triggering receptor expressed on myeloid cells (TREM)-1 is a recently identified immunoglobulin receptor that is expressed on neutrophils and monocytes where it amplifies the acute inflammatory response to bacteria. We examined the transcriptional regulation of TREM-1 in macrophages. Treatment of RAW cells with Escherichia coli LPS or Pseudomonas aeruginosa led to the induction of TREM-1 within 1 h with an expression lasting up to at least 24 h in vitro as detected by RT-PCR. Since the promoter of TREM-1 has multiple binding sites for NF-kappa B and PU.1 (one of the members of the ets family of transcription factors), we investigated the role of these transcription factors in the induction of TREM-1. Treatment of cells with NF-kappa B inhibitors abolished the expression of message of TREM-1 induced by LPS and P. aeruginosa. In contrast, the expression of TREM-1 was increased after stimulation with LPS or P. aeruginosa in cells that had gene of PU.1 silenced. Additionally, over-expression of PU.1 led to inhibition of TREM-1 induction in response to LPS and P. aeruginosa. These data suggest that both these transcription factors are involved in the expression of TREM-1. NF-kappa B functions as a positive regulator whereas PU.1 is a negative regulator of the TREM-1 gene.