Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma.
Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma.
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DOI：
10.1183/09031936.00068712
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Kraft M
中科院分区：
文献类型：
--
作者：
Firszt R;Francisco D;Church TD;Thomas JM;Ingram JL;Kraft M
呼吸道重塑是哮喘的一个特征，导致肺功能丧失。气道重塑的核心成分之一是上皮下纤维化。白介素13(IL-13)是一种关键的T辅助细胞因子，被认为是包括重塑在内的过敏性哮喘的中枢介质，但在人类哮喘中驱动后者的机制尚未阐明。我们推测，与健康对照组相比，IL-13以基质金属蛋白酶和转化生长因子β1依赖的方式刺激哮喘患者的气道成纤维细胞产生1型胶原。从14例轻度哮喘患者和13例接受支气管镜检查的正常对照的支气管内活检组织中培养成纤维细胞。用不同的介质包括IL-13和特异性的基质金属蛋白酶抑制物处理气道成纤维细胞。与正常对照组相比，IL-13显著刺激哮喘患者I型胶原的产生。基质金属蛋白酶-2的抑制剂显著减少哮喘患者的胶原生成，但对正常对照组无效。IL-13显著增加转化生长因子-MMP1的总形式和活性形式，这种激活可被β-2抑制剂阻断。IL-13激活内源性基质金属蛋白酶-2哮喘患者与正常对照组比较。在体外模型中，IL-13通过涉及转化生长因子-β-1和基质金属蛋白酶-2的机制来增强气道重塑。这些效应提供了对IL-13指导哮喘气道重塑的机制的洞察力。
Airway remodelling is a feature of asthma that contributes to loss of lung function. One of the central components of airway remodelling is subepithelial fibrosis. Interleukin (IL)-13 is a key T-helper 2 cytokine and is believed to be the central mediator of allergic asthma including remodelling, but the mechanism driving the latter has not been elucidated in human asthma. We hypothesised that IL-13 stimulates collagen type-1 production by the airway fibroblast in a matrix metalloproteinase (MMP)- and transforming growth factor (TGF)-β1-dependent manner in human asthma as compared to healthy controls. Fibroblasts were cultured from endobronchial biopsies in 14 subjects with mild asthma and 13 normal controls that underwent bronchoscopy. Airway fibroblasts were treated with various mediators including IL-13 and specific MMP-inhibitors. IL-13 significantly stimulated collagen type-1 production in asthma compared to normal controls. Inhibitors of MMP-2 significantly attenuated collagen production in asthma but had no effect in normal controls. IL-13 significantly increased total and active forms of TGF-β1, and this activation was blocked using an MMP-2 inhibitor. IL-13 activated endogenous MMP-2 in asthma patients as compared to normal controls. In an ex vivo model, IL-13 potentiates airway remodelling through a mechanism involving TGF-β1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed airway remodelling in asthma.
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影响因子：
2.9
作者：
ABE, M;HARPEL, JG;RIFKIN, DB
通讯作者：
RIFKIN, DB
影响因子：
10.4
作者：
LAST, JA;REISER, KM
通讯作者：
REISER, KM
影响因子：
8.3
作者：
Petrov, VV;Fagard, RH;Lijnen, PJ
通讯作者：
Lijnen, PJ
影响因子：
5.8
作者：
Malavia NK;Mih JD;Raub CB;Dinh BT;George SC
通讯作者：
George SC
DOI：
10.1084/jem.194.6.809
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee CG;Homer RJ;Zhu Z;Lanone S;Wang X;Koteliansky V;Shipley JM;Gotwals P;Noble P;Chen Q;Senior RM;Elias JA
通讯作者：
Elias JA