Eosinophil-associated TGF-beta(1) mRNA expression and airways fibrosis in bronchial asthma
Eosinophil-associated TGF-beta(1) mRNA expression and airways fibrosis in bronchial asthma
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DOI：
10.1165/ajrcmb.17.3.2733
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发表时间：
1997-09-01
影响因子：
6.4
通讯作者：
Hamid, Q
中科院分区：
文献类型：
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作者：
Minshall, EM;Leung, DYM;Hamid, Q
支气管哮喘的组织病理学与气道内的结构改变有关，包括上皮下纤维化和慢性嗜酸性粒细胞炎症。负责这种组织重塑的机制，特别是炎症细胞的作用，仍有待确定。转化生长因子- β (tgf - β)是一种有效的促纤维化细胞因子，可能通过胶原纤维的沉积导致网状膜增厚。为了研究这些结构变化的分子机制，我们利用原位杂交和免疫细胞化学技术研究了轻至重度哮喘患者和正常对照组支气管黏膜中tgf - β (1) mRNA的表达和免疫反应性。由于嗜酸性粒细胞在哮喘气道内非常突出，并且可以合成促炎细胞因子，因此我们还检测了嗜酸性粒细胞中tgf - β (1) mRNA和免疫反应蛋白的存在，哮喘个体在气道粘膜下层中tgf - β (1) mRNA和免疫反应性的表达高于正常对照组（P < 0.05），并且这些增加与疾病的严重程度直接相关。通过组织化学检测，哮喘患者的气道纤维化程度也比正常对照组增加（P < 0.005）。在哮喘受试者中，上皮下纤维化的存在与疾病的严重程度相关，并与1 s内用力呼气量的下降相关(r(2) = 0.78；P < 0.05)。在哮喘气道内，eg2阳性嗜酸性粒细胞是tgf - β (1) mRNA和免疫反应性的主要来源。这些结果证明，tgf - β(1)可能在哮喘气道内发生的纤维化变化中发挥作用，激活的嗜酸性粒细胞是这种细胞因子的主要来源。
The histopathology of bronchial asthma is associated with structural changes within the airways, including subepithelial fibrosis, as well as chronic eosinophilic inflammation. The mechanisms responsible for this tissue remodeling, and in particular the role of inflammatory cells, remain to be established. Transforming growth factor-beta (TGF-beta) is a potent profibrotic cytokine which may contribute to the thickening of the reticular lamina by the deposition of collagen fibers, To investigate the molecular mechanisms underlying these structural changes, we have investigated the expression of TGF-beta(1) mRNA and immunoreactivity within the bronchial mucosa of mild to severe asthmatic individuals and normal control subjects using the techniques of in situ hybridization and immunocytochemistry. As eosinophils are prominent within the asthmatic airway and are known to synthesize pro-inflammatory cytokines, the presence of TGF-beta(1) mRNA and immunoreactive protein in eosinophils was also examined, Asthmatic individuals exhibited a greater expression of TGF-beta(1) mRNA and immunoreactivity in the airways submucosa than normal control subjects (P < 0.05), and these increases were directly related to the severity of the disorder. The extent of airways fibrosis, as detected histochemically, was also increased in asthmatics compared with normal control subjects (P < 0.005). In asthmatic subjects, the presence of subepithelial fibrosis was associated with the severity of the disease and correlated with the decline in forced expiratory volume in 1 s (r(2) = 0.78; P < 0.05). Within the asthmatic airways, EG2-positive eosinophils represented the major source of TGF-beta(1) mRNA and immunoreactivity. These results provide evidence that TGF-beta(1) may play a role in the fibrotic changes occurring within asthmatic airways and that activated eosinophils are a major source of this cytokine.