Simultaneous stimulation with TGF-β1 and TNF-α induces epithelial mesenchymal transition in bronchial epithelial...

Airway remodeling is an important feature of chronic airway disease, but the mechanisms involved remain unclear. Recently, epithelial mesenchymal transition (EMT) was reported to be associated with tissue fibrosis. TGF-β1, which is a potent inducer of EMT, is thought to be related to the pathogenesis of airway remodeling. We investigated whether TGF-β1 and/or TNF-α induce EMT in bronchial epithelial cells.

Cultured BEAS-2B cells and primary normal human bronchial epithelial cells (NHBE) were treated with TGF-β1 and/or TNF-α. Morphological changes and the expression of EMT-related markers were evaluated by immunocytochemical staining. Expressions of EMT-related markers, extracellular matrix (ECM) components (collagen type I and versican), and TGF-β receptors I, II, and III were analyzed by quantitative RT-PCR. Migration was evaluated using the Boyden chamber technique.

The TGF-β1-induced EMT in BEAS-2B cells was demonstrated on the basis of morphological changes and the downregulation of E-cadherin. Costimulation with TNF-α enhanced the TGF-β1-induced morphological changes and increased vimentin expression. Treatment with TGF-β1 increased the expression of collagen type I and versican. EMT induced with TGF-β1 plus TNF-α promoted cell migration. Stimulation of NHBE with TGF-β1 led to EMT.

TGF-β1 induced EMT in BEAS-2B cells, and costimulation with TNF-α enhanced the EMT. As a result of the EMT process, BEAS-2B cells acquired functions of mesenchymal cells. In addition, TGF-β1 treatment induced EMT in NHBE as shown by changes in EMT-related markers. Bronchial epithelial cells might contribute to airway remodeling through EMT.