IL-1ß 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, 2014 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-24186874
ABSTRACT
Perinatal inflammation and the inflammatory cytokine IL-1 can modify lung morphogenesis. To examine the effects of antenatal expression of IL-1ß in the distal airway epithelium on fetal lung morphogenesis, we studied lung development and surfactant expression in fetal mice expressing human IL-1ß under the control of the surfactant protein (SP)-C promoter. IL-1ß-expressing pups suffered respiratory failure and died shortly after birth. IL-1ß 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-1ß 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-1ß 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-1ß-expressing fetal mice. IL-1ß 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-1ß 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-1ß. In conclusion, expression of IL-1ß 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Respiratória
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Diferenciação Celular
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Interleucina-1beta
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Células Epiteliais Alveolares
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Pulmão
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Morfogênese
Limite:
Animals
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article