The Lipocalin2 Gene is Regulated in Mammary Epithelial Cells by NFκB and C/EBP In Response to Mycoplasma.
The Lipocalin2 Gene is Regulated in Mammary Epithelial Cells by NFκB and C/EBP In Response to Mycoplasma.
复制标题
Lipocalin2 基因在乳腺上皮细胞中由 NFκB 和 C/EBP 调节以响应支原体。
DOI：
10.1038/s41598-020-63393-x
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发表时间：
2020
影响因子：
4.6
通讯作者：
Nilsen-Hamilton,Marit
中科院分区：
文献类型：
--
作者：
Zhao,Wei;Bendickson,Lee;Nilsen-Hamilton,Marit
Lcn2 基因表达随着细胞应激信号的增加而增加，特别是在参与先天免疫反应的细胞中。人类 Lcn2 (NGAL) 在血液和组织中增加，以应对许多应激源，包括微生物感染以及骨髓和上皮细胞中的 LPS。在这里，我们将 Lcn2 的微生物激活剂扩展到支原体，并描述了在小鼠乳腺上皮细胞中研究 MALP-2 和支原体感染对 Lcn2 基因调节机制的研究。对于骨髓细胞的 LPS 反应，上皮细胞中 Lcn2 表达先于 TNFα、IL-6 和 IκB z 表达增加，选择性减少 IκB z 会降低 Lcn2 启动子活性。 Lcn2 启动子激活在暴露于 MALP-2 后仍保持升高，并且在支原体感染的细胞中持续升高。人类或小鼠 Lcn2 启动子的激活需要 NFκB 和 C/EBP 的激活。因此，Lcn2 被支原体成分强烈而持久地激活，通过与人类和小鼠基因相同的基本调节机制刺激先天免疫反应。
Lcn2 gene expression increases in response to cell stress signals, particularly in cells involved in the innate immune response. Human Lcn2 (NGAL) is increased in the blood and tissues in response to many stressors including microbial infection and in response to LPS in myeloid and epithelial cells. Here we extend the microbial activators of Lcn2 to mycoplasma and describe studies in which the mechanism of Lcn2 gene regulation by MALP-2 and mycoplasma infection was investigated in mouse mammary epithelial cells. As for the LPS response of myeloid cells, Lcn2 expression in epithelial cells is preceded by increased TNFα, IL-6 and IκBζ expression and selective reduction of IκBζ reduces Lcn2 promoter activity. Lcn2 promoter activation remains elevated well beyond the period of exposure to MALP-2 and is persistently elevated in mycoplasma infected cells. Activation of either the human or the mouse Lcn2 promoter requires both NFκB and C/EBP for activation. Thus, Lcn2 is strongly and enduringly activated by mycoplasma components that stimulate the innate immune response with the same basic regulatory mechanism for the human and mouse genes.