| First Author | Hogmalm A | Year | 2014 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 306 |
| Issue | 1 | Pages | L23-34 |
| PubMed ID | 24186874 | Mgi Jnum | J:210908 |
| Mgi Id | MGI:5572867 | Doi | 10.1152/ajplung.00154.2013 |
| Citation | Hogmalm A, et al. (2014) IL-1beta expression in the distal lung epithelium disrupts lung morphogenesis and epithelial cell differentiation in fetal mice. Am J Physiol Lung Cell Mol Physiol 306(1):L23-34 |
| abstractText | Perinatal inflammation and the inflammatory cytokine IL-1 can modify lung morphogenesis. To examine the effects of antenatal expression of IL-1beta in the distal airway epithelium on fetal lung morphogenesis, we studied lung development and surfactant expression in fetal mice expressing human IL-1beta under the control of the surfactant protein (SP)-C promoter. IL-1beta-expressing pups suffered respiratory failure and died shortly after birth. IL-1beta caused fetal lung inflammation and enhanced the expression of keratinocyte-derived chemokine (KC/CXCL1) and monocyte chemoattractant protein 3 (MCP-3/CCL7), the calgranulins S100A8 and S100A9, the acute-phase protein serum amyloid A3, the chitinase-like proteins Ym1 and Ym2, and pendrin. IL-1beta decreased the percentage of the total distal lung area made up of air saccules and the number of air saccules in the lungs of fetal mice. IL-1beta inhibited the expression of VEGF-A and its receptors VEGFR-1 and VEGFR-2. The percentage of the cellular area of the distal lung made up of capillaries was decreased in IL-1beta-expressing fetal mice. IL-1beta suppressed the production of SP-B and pro-SP-C and decreased the amount of phosphatidylcholine and the percentage of palmitic acid in the phosphatidylcholine fraction of lung phospholipids, indicating that IL-1beta prevented the differentiation of type II epithelial cells. The production of Clara cell secretory protein in the nonciliated bronchiolar (Clara) cells was likewise suppressed by IL-1beta. In conclusion, expression of IL-1beta in the epithelium of the distal airways disrupted the development of the airspaces and capillaries in the fetal lung and caused fatal respiratory failure at birth. |
