Caveolin1 interacts with the glucocorticoid receptor in the lung but is dispensable for its anti-inflammatory actions in lung inflammation and Trichuris Muris infection.
Caveolin1 interacts with the glucocorticoid receptor in the lung but is dispensable for its anti-inflammatory actions in lung inflammation and Trichuris Muris infection.
复制标题
Caveolin1 与肺部的糖皮质激素受体相互作用，但其在肺部炎症和鞭毛虫感染中的抗炎作用是可有可无的。
DOI：
10.1038/s41598-019-44963-0
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发表时间：
2019
影响因子：
4.6
通讯作者：
Caratti G
中科院分区：
文献类型：
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作者：
Caratti G
糖皮质激素（Gcs）是一种广泛使用的抗炎化合物，通过糖皮质激素受体（GR）起作用。通过在肺组织中进行无偏倚的蛋白质组学筛选，我们发现膜蛋白caveolin -1 （Cav1）是GR的直接相互作用伙伴。与对照组相比，inav1基因敲除小鼠的GR更能激活抗炎基因，包括dusp1。因此，我们确定了Cav1在两种肺部炎症模型中调节Gc作用的作用。我们首先测试了肺部的先天反应。cav1的缺失损害了炎症对雾化LPS的反应，增加了肺细胞因子/趋化因子的分泌，但损害了中性粒细胞的浸润。尽管炎症反应发生了这些变化，但对Gcs的抗炎能力没有影响。我们还在过敏性气道炎症模型中测试了GR/Cav1串扰。cav1对炎症反应有非常轻微的影响，但对Gc反应没有影响——两种基因型之间的免疫细胞浸润（巨噬细胞、嗜酸性粒细胞、中性粒细胞）、病理评分和PAS阳性细胞相当。进一步研究Th2适应性免疫反应，我们证明cav1敲除小鼠保留了驱逐肠道线虫寄生虫et的能力。它需要适应性Th2免疫反应来消除。因此，Cav1调节肺部的先天免疫应答，但对肺部或肠道中th2介导的适应性免疫没有影响。虽然我们证明了Cav1调节抗炎基因的GR反激活，但这并不能在体内转化为抑制炎症的作用。
Glucocorticoids (Gcs) are widely prescribed anti-inflammatory compounds, which act through the glucocorticoid receptor (GR). Using an unbiased proteomics screen in lung tissue, we identified the membrane protein caveolin -1 (Cav1) as a direct interaction partner of the GR. InCav1knockout mice GR transactivates anti-inflammatory genes, includingDusp1, more than in controls. We therefore determined the role of Cav1 in modulating Gc action in two models of pulmonary inflammation. We first tested innate responses in lung. Loss ofCav1impaired the inflammatory response to nebulized LPS, increasing cytokine/chemokine secretion from lung, but impairing neutrophil infiltration. Despite these changes to the inflammatory response, there was noCav1effect on anti-inflammatory capacity of Gcs. We also tested GR/Cav1 crosstalk in a model of allergic airway inflammation.Cav1had a very mild effect on the inflammatory response, but no effect on the Gc response – with comparable immune cell infiltrate (macrophage, eosinophils, neutrophils), pathological score and PAS positive cells observed between both genotypes. Pursuing the Th2 adaptive immune response further we demonstrate thatCav1knockout mice retained their ability to expel the intestinal nematode parasiteT.muris, which requires adaptive Th2 immune response for elimination. Therefore, Cav1 regulates innate immune responses in the lung, but does not have an effect on Th2-mediated adaptive immunity in lung or gut. Although we demonstrate that Cav1 regulates GR transactivation of anti-inflammatory genes, this does not translate to an effect on suppression of inflammationin vivo.