Enteric expression of the integrin αvβ6 is essential for nematode-induced mucosal mast cell hyperplasia and expression of the granule chymase, mouse mast cell protease-1
Enteric expression of the integrin αvβ6 is essential for nematode-induced mucosal mast cell hyperplasia and expression of the granule chymase, mouse mast cell protease-1
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DOI：
10.1016/s0002-9440(10)64236-8
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发表时间：
2002-09-01
影响因子：
6
通讯作者：
Miller, HRP
中科院分区：
文献类型：
--
作者：
Knight, PA;Wright, SH;Miller, HRP
免疫调节性细胞因子转化生长因子(TGF)- β(1)是一种具有潜伏相关肽的生物无活性复合物，必须经过局部因子修饰才能暴露出具有功能活性的细胞因子。上皮整合素α (v) β(6)介导肺中tgf - β(1)的局部激活，β(6)（-/-）小鼠表现出夸大的肺部炎症，但它们对肠道炎症刺激的反应尚未被研究。我们发现β(6)和tgf - β(1)在未感染的小鼠和感染巴西尼波圆线虫的小鼠空肠上皮间室中组成性表达。我们还提供的数据显示，β(6)（-/-）小鼠在感染后产生粘膜肥大细胞反应的能力严重受损，颗粒酶（小鼠肥大细胞蛋白酶-1）的表达和全身释放显著减少。由于这种酶的体外表达受tgf - β(1)的调节，这些数据表明，在缺乏α (v) β(6)的情况下，上皮表达的tgf - β(1)可能不会被激活，从而导致小鼠肥大细胞蛋白酶-1的表达缺失和粘膜肥大细胞反应的下调。
The immunoregulatory cytokine transforming growth factor (TGF)-beta(1) is secreted as a biologically inactive complex with latency-associated peptide, which must be modified by local factors to expose the functionally active cytokine. The epithelial integrin alpha(v)beta(6) mediates local activation of TGF-beta(1) in the lung and beta(6)(-/-) mice exhibit exaggerated pulmonary inflammation, but their response to inflammatory stimuli in the gut has not been investigated. We found that both beta(6) and TGF-beta(1) are constitutively expressed in the jejunal epithelial compartment in uninfected mice and during infection with the intestinal nematode Nippostrongylus brasiliensis. We also present data showing that beta(6)(-/-) mice are seriously compromised in their ability to mount a mucosal mast cell response after infection, and there is a significant reduction in the expression and systemic release of the granule chymase, mouse mast cell protease-1. Because in vitro expression of this chymase is regulated by TGF-beta(1), these data indicate that in the absence of alpha(v)beta(6) epithelially expressed TGF-beta(1) may not be activated, with a consequent absence of expression of mouse mast cell protease-1 and down-regulation of the mucosal mast cell response.