TNF-alpha downregulates the leukotriene C4 synthase gene in mononuclear phagocytes.
TNF-alpha downregulates the leukotriene C4 synthase gene in mononuclear phagocytes.
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TNF-α 下调单核吞噬细胞中的白三烯 C4 合酶基因。
DOI：
10.1152/ajplung.00023.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Mao,JennyT
中科院分区：
文献类型：
--
作者：
Serio,KennethJ;Luo,Colin;Luo,Linda;Mao,JennyT
We studied the effect of tumor necrosis factor (TNF)-α exposure on cysteinyl leukotriene (LT) synthesis by cells of monocyte/macrophage lineage. TNF-α conditioning of monocytic THP-1 cells and primary human monocytes resulted in a decreased capacity for LTC4release. TNF-α exposure (for 16–24 h) decreased LTC4synthase mRNA in THP-1 cells, primary mouse bone marrow-derived macrophages, and eosinophilic AML14.3D10 cells. TNF-α downregulated LTC4synthase mRNA in THP-1 cells in a dose- and time-dependent manner, with downregulation observed as early as 4 h. The effect of TNF-α on LTC4synthase mRNA expression was mediated via the MEK/ERK pathway, but not via cyclooxygenase or nitric oxide synthase pathways. Conditioning of actinomycin D-treated cells with TNF-α did not accelerate degradation of LTC4synthase mRNA. TNF-α produced sustained activation of p50 and p65, which were previously reported by our group to decrease LTC4synthase promoter activity. In transiently transfected THP-1 cells, TNF-α decreased promoter activity via an element located within the first 620 bp of the promoter. We conclude that TNF-α exposure downregulates the synthetic capacity for cysteinyl LT release and LTC4synthase gene expression in monocytes/macrophages via a transcriptional mechanism.
