Tumor necrosis factor-alpha enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-beta1.
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.
Yamauchi
Yasuhiro
Y
Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan. YAMAUCHIY-INT@h.u-tokyo.ac.jp
Kohyama
Tadashi
T
Takizawa
Hajime
H
Kamitani
Sumiko
S
Desaki
Masashi
M
Takami
Kazutaka
K
Kawasaki
Shin
S
Kato
Jun
J
Nagase
Takahide
T
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000473:pathology*; D054337:Cell Dedifferentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis / Q000209:etiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha