Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1).
Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1).
复制标题
DOI：
10.1084/jem.194.6.809
复制
发表时间：
2001-09-17
期刊：
影响因子：
--
通讯作者：
Elias JA
中科院分区：
文献类型：
--
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
白细胞介素（IL）-13是由T辅助细胞2型炎症引起的组织纤维化的关键介质。我们假设IL-13的纤维化作用是由转化生长因子（TGF）-β介导的。为了验证这一假设，我们比较了野生型小鼠和IL-13过表达导致肺纤维化的CC 10-IL-13小鼠肺中TGF-β的调节。IL-13选择性刺激转基因动物产生TGF-β1，巨噬细胞是TGF-β1在这些组织中产生和沉积的主要部位。IL-13还在体内激活TGF-β1。这种激活与编码潜伏性TGF-β结合蛋白-1的mRNA水平降低和编码尿纤溶酶原激活物、基质金属蛋白酶（MMP）-9和CD 44的mRNA水平升高相关。纤溶酶/丝氨酸蛋白酶拮抗剂抑肽酶可抑制TGF-β1的活化。在CC 10-IL-13小鼠和MMP-9缺失小鼠的杂交后代中也降低，但在与CD 44缺失动物的杂交中没有改变。用TGF-β拮抗剂可溶性TGFβR-Fc（sTGFβ R-Fc）治疗也显著改善了IL-13诱导的纤维化。这些研究表明，IL-13是体内TGF-β1的有效刺激剂和激活剂。他们还证明，这种激活是由纤溶酶/丝氨酸蛋白酶和MMP-9依赖性和CD 44非依赖性机制介导的，并且IL-13的纤维化作用在很大程度上是由这种TGF-β途径介导的。
Interleukin (IL)-13 is a key mediator of tissue fibrosis caused by T helper cell type 2 inflammation. We hypothesized that the fibrogenic effects of IL-13 are mediated by transforming growth factor (TGF)-β. To test this hypothesis we compared the regulation of TGF-β in lungs from wild-type mice and CC10-IL-13 mice in which IL-13 overexpression causes pulmonary fibrosis. IL-13 selectively stimulated TGF-β1 production in transgenic animals and macrophages were the major site of TGF-β1 production and deposition in these tissues. IL-13 also activated TGF-β1 in vivo. This activation was associated with decreased levels of mRNA encoding latent TGF-β–binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44. TGF-β1 activation was abrogated by the plasmin/serine protease antagonist aprotinin. It was also decreased in progeny of crosses of CC10-IL-13 mice and MMP-9 null mice but was not altered in crosses with CD44 null animals. IL-13–induced fibrosis was also significantly ameliorated by treatment with the TGF-β antagonist soluble TGFβR-Fc (sTGFβR-Fc). These studies demonstrate that IL-13 is a potent stimulator and activator of TGF-β1 in vivo. They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9–dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-β pathway.
登录
查看更多内容
DOI：
10.1006/clin.1997.4409
发表时间：
1997-09-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
Letterio, JJ;Roberts, AB
通讯作者：
Roberts, AB
DOI：
10.1165/ajrcmb/5.2.155
发表时间：
1991-08-01
影响因子：
6.4
作者：
KHALIL, N;OCONNOR, RN;GREENBERG, AH
通讯作者：
GREENBERG, AH
DOI：
10.1073/pnas.96.22.12719
发表时间：
1999-10-26
影响因子：
11.1
作者：
George, J;Roulot, D;Bissell, DM
通讯作者：
Bissell, DM
DOI：
10.1165/ajrcmb.15.2.8703482
发表时间：
1996-08-01
影响因子：
6.4
作者：
Khalil, N;Corne, S;Yacyshyn, H
通讯作者：
Yacyshyn, H
影响因子：
4.4
作者：
Hoffmann, KF;Cheever, AW;Wynn, TA
通讯作者：
Wynn, TA