Inhibition of the transcription factors NF-kappa B and AP-1 underlies loss of cytokine gene expression in rat alveolar macrophages treated with a diffusible product from the spores of Aspergillus fumigatus
Inhibition of the transcription factors NF-kappa B and AP-1 underlies loss of cytokine gene expression in rat alveolar macrophages treated with a diffusible product from the spores of Aspergillus fumigatus
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DOI：
10.1165/ajrcmb.15.1.8679226
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发表时间：
1996-07-01
影响因子：
6.4
通讯作者：
Donaldson, K
中科院分区：
文献类型：
--
作者：
Nicholson, WJ;Slight, J;Donaldson, K
烟曲霉的孢子在肺部比其他可呼吸真菌孢子具有生存优势，导致许多与这种真菌相关的肺部疾病。我们假设孢子表面的一种成分可以抑制肺泡巨噬细胞的活化，已知肺泡巨噬细胞在肺部免疫调节中发挥重要作用。在酶联免疫吸附测定中，烟曲霉 (AfD) 孢子的可扩散产物抑制肺泡巨噬细胞产生肿瘤坏死因子 α (TNF α) 蛋白。使用半定量逆转录聚合酶链反应，我们还证明了 AfD 对大鼠肺泡巨噬细胞中促炎细胞因子转录物的产生具有有效的抑制作用。这种抑制发生在转录水平，AfD 抑制 TNF α 和白细胞介素 6 (IL-6) 特异性 mRNA 转录物的合成。未发现对白细胞介素 1 β (IL-1 β) 细胞因子转录物的合成或管家基因 β-肌动蛋白的表达有影响。此外，AfD 特异性抑制核转录因子 NF-κ B 和 AP-1 的激活，这两种因子都是协调上调促炎细胞因子 TNF α、IL-1 β 和 IL-6 转录所必需的。我们得出结论，AfD可以通过选择性抑制关键炎症细胞因子的产生来抑制正常的肺泡巨噬细胞反应，并且抑制机制主要在转录激活水平。
The spores of Aspergillus fumigatus have a survival advantage over other respirable fungal spores in the lung, leading to a number of lung diseases associated with this fungus. We have hypothesized that a component on the spore surface can inhibit the activation of alveolar macrophages, known to play an essential role in immune regulation in the lung. A diffusible product from the spores of A. fumigatus (AfD) inhibited the production of tumor necrosis factor alpha (TNF alpha) protein by alveolar macrophages in an enzyme-linked immune sorbent assay. Using a semiquantitative reverse transcription-polymerase chain reaction, we also demonstrated a potent inhibitory effect of AfD on the production of proinflammatory cytokine transcripts in rat alveolar macrophages. The inhibition occurred at the level of transcription, with AfD inhibiting the synthesis of TNF alpha- and interleukin 6 (IL-6)-specific mRNA transcripts. No effect was seen on the synthesis of interleukin 1 beta (IL-1 beta) cytokine transcripts or on the expression of the housekeeping gene beta-actin. Furthermore, AfD specifically inhibited the activation of nuclear transcription factors NF-kappa B and AP-1, both of which are required for the coordinate upregulation of transcription sf the proinflammatory cytokines TNF alpha, IL-1 beta, and IL-6. We conclude that AfD can inhibit normal alveolar macrophage responses by selectively inhibiting the production of key inflammatory cytokines, and that the mechanism of inhibition is primarily at the level of transcriptional activation.