Back to Search
Start Over
Tumor necrosis factor-alpha enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-beta1.
- Source :
-
Experimental lung research [Exp Lung Res] 2010 Feb; Vol. 36 (1), pp. 12-24. - Publication Year :
- 2010
-
Abstract
- Recently, epithelial-mesenchymal transition (EMT) has been reported to contribute to tissue fibrosis through enhanced transforming growth factor (TGF)-beta1 signaling. Tumor necrosis factor (TNF)-alpha has also been implicated in tissue fibrosis. Therefore, the authors investigated whether TNF-alpha affected TGF-beta1-induced EMT. Cultured alveolar epithelial cells (A549 cells) were stimulated with TGF-beta1 (5 ng/mL), with/without TNF-alpha (10 ng/mL). TGF-beta1 induced EMT of A549 cells, with loss of E-cadherin and acquisition of vimentin. Combination of TNF-alpha with TGF-beta1 enhanced EMT, causing morphological changes, while quantitative polymerase chain reaction (PCR) showed suppression of E-cadherin mRNA and expression of vimentin mRNA. In addition, the gel contraction method revealed that cells that had undergone EMT acquired cell contractility, which is a feature of mesenchymal cells. Stimulation with TGF-beta1 induced cell contraction, as did TNF-alpha. Moreover, costimulation with TGF-beta1 and TNF-alpha enhanced the cell contraction. Although IFN-gamma suppressed spontaneous cell contraction, it did not suppress cell contraction, which was induced by TGF-beta1. In conclusion, TNF-alpha enhances not only EMT but also cell contraction induced by TGF-beta1. EMT might contribute to tissue fibrosis through induction of cell contraction.
- Subjects :
- Cell Line, Tumor
Epithelial Cells drug effects
Epithelial Cells pathology
Fibrosis etiology
Humans
Mesenchymal Stem Cells pathology
Adenocarcinoma, Bronchiolo-Alveolar pathology
Cell Dedifferentiation drug effects
Cell Shape drug effects
Transforming Growth Factor beta1 pharmacology
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0499
- Volume :
- 36
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental lung research
- Publication Type :
- Academic Journal
- Accession number :
- 20128678
- Full Text :
- https://doi.org/10.3109/01902140903042589