IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice.
IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice.
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DOI：
10.4049/jimmunol.163.3.1529
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发表时间：
1999-08
影响因子：
4.4
通讯作者：
C. Salkowski;K. Kopydlowski;J. Blanco;M. J. Cody;R. McNally;S. Vogel
中科院分区：
文献类型：
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作者：
C. Salkowski;K. Kopydlowski;J. Blanco;M. J. Cody;R. McNally;S. Vogel
利用来自IFN-调节因子-1（IRF-1）和IRF-2敲除（-/-）和野生型（+/+）小鼠的巨噬细胞来检查这些转录因子在IL-12 mRNA和蛋白表达的调节中的作用。LPS对IRF-1（-/-）和IRF-2（-/-）巨噬细胞IL-12 p40 mRNA的诱导作用明显减弱。相反，IRF-1（-/-），而不是IRF-2（-/-），巨噬细胞表现出受损的LPS诱导的IL-12 p35 mRNA表达。当两种刺激物同时存在时，IFN-γ进一步增加LPS诱导的IL-12 p40 mRNA的能力在IRF-1（-/-）和IRF-2（-/-）巨噬细胞中均显著降低，在IRF-1（-/-）巨噬细胞中观察到最严重的损伤。在IRF-1（-/-）和IRF-2（-/-）巨噬细胞中，LPS或LPS + IFN-γ刺激后IL-12 mRNA表达的降低伴随着IL-12 p40和IL-12 p70蛋白的显著降低。在LPS处理之前，用IFN-γ致敏IRF-1（-/-）和IRF-2（-/-）巨噬细胞24小时，部分恢复IRF-1（-/-）和IRF-2（-/-）巨噬细胞中受损的IL-12 mRNA和蛋白质产生。IRF-1（-/-）和IRF-2（-/-）巨噬细胞中IFN-γ mRNA表达的显著降低可抑制IL-12水平的降低。这些结果表明，IRF-1和IRF-2都是调节巨噬细胞IL-12和IFN-γ产生的关键转录因子。
Macrophages derived from IFN-regulatory factor-1 (IRF-1) and IRF-2 knockout (-/-) and wild-type (+/+) mice were utilized to examine the role of these transcription factors in the regulation of IL-12 mRNA and protein expression. Induction of IL-12 p40 mRNA by LPS was markedly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages. In contrast, IRF-1(-/-), but not IRF-2(-/-), macrophages exhibited impaired LPS-induced IL-12 p35 mRNA expression. The ability of IFN-gamma to augment LPS-induced IL-12 p40 mRNA further when both stimuli were present simultaneously was significantly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages, with the most profound impairment observed for IRF-1(-/-) macrophages. Reductions in IL-12 mRNA expression after stimulation with LPS or LPS plus IFN-gamma were accompanied by substantial reductions in IL-12 p40 and IL-12 p70 protein in both IRF-1(-/-) and IRF-2(-/-) macrophages. Priming IRF-1(-/-) and IRF-2(-/-) macrophages with IFN-gamma for 24 h before LPS treatment partially restored impaired IL-12 mRNA and protein production in both IRF-1(-/-) and IRF-2(-/-) macrophages. Depressed IL-12 levels were paralleled by significant reductions in IFN-gamma mRNA expression in IRF-1(-/-) and IRF-2(-/-) macrophages. These results indicate that both IRF-1 and IRF-2 are critical transcription factors in the regulation of macrophage IL-12 and consequently IFN-gamma production.