IL-1β disrupts postnatal lung morphogenesis in the mouse
IL-1β disrupts postnatal lung morphogenesis in the mouse
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DOI：
10.1165/rcmb.2006-0116oc
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发表时间：
2007-01-01
影响因子：
6.4
通讯作者：
Lappalainen, Urpo
中科院分区：
文献类型：
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作者：
Bry, Kristina;Whitsett, Jeffrey A.;Lappalainen, Urpo
肺部炎症和炎性细胞因子IL-1 β的产生增加与早产儿支气管肺发育不良（BPD）的发生有关。为了研究IL-1 β在体内胎儿和新生儿肺中的作用，我们开发了一种双转基因小鼠，其中IL-1 β在条件控制下在气道上皮细胞中表达。围产期肺部IL-1 β表达导致呼吸功能不全，与出生后死亡率增加相关。虽然IL-1 β表达小鼠的宫内生长是正常的，但它们的出生后生长受损。IL-1 β破坏了肺泡间隔，并导致远端气隙间隔中α-平滑肌肌动蛋白和弹性蛋白沉积异常。IL-1 β干扰毛细血管发育，抑制幼鼠肺血管内皮生长因子的产生。IL-1 β诱导了CXC趋化因子KC（CXCL 1）和巨噬细胞炎性蛋白-2（CXCL 2）以及CC趋化因子单核细胞趋化蛋白（MCP）-1（CCL 2）和MCP-3（CCL 7）的表达，这与肺的嗜中性粒细胞和单核细胞浸润一致。IL-1 β引起杯状细胞化生和支气管平滑肌增生。围产期肺上皮细胞中IL-1 β的表达引起了一种在临床和组织学上与BPD相似的肺部疾病。
Pulmonary inflammation and increased production of the inflammatory cytokine IL-1 beta are associated with the development of bronchopulmonary dysplasia (BPD) in premature infants. To study the actions of IL-1 beta in the fetal and newborn lung in vivo, we developed a bitransgenic mouse in which IL-1 beta is expressed under conditional control in airway epithelial cells. Perinatal pulmonary expression of IL-1 beta caused respiratory insufficiency that was associated with increased postnatal mortality. While intrauterine growth of IL-1 beta expressing mice was normal, their postnatal growth was impaired. IL-1 beta disrupted alveolar septation and caused abnormalities in alpha-smooth muscle actin and elastin deposition in the septa of distal airspaces. IL-1 beta disturbed capillary development and inhibited the production of vascular endothelial growth factor in the lungs of infant mice. IL-1 beta induced the expression of CXC chemokines KC (CXCL1) and macrophage inflammatory protein-2 (CXCL2) and of CC chemokines monocyte chemotactic protein (MCP)-1 (CCL2) and MCP-3 (CCL7), consistent with neutrophilic and monocytic infiltration of the lungs. IL-1 beta caused goblet cell metaplasia and bronchial smooth muscle hyperplasia. Perinatal expression of IL-1 beta in epithelial cells of the lung caused a lung disease that was clinically and histologically similar to BPD.