Inflammatory cytokines augments TGF-β1-induced epithelial-mesenchymal transition in A549 cells by up-regulating TβR-I

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Abstract

Epithelial-mesenchymal transition (EMT) is believed to play an important role in fibrosis and tumor invasion. EMT can be induced in vitro cell culture by various stimuli including growth factors and matrix metalloproteinases. In this study, we report that cytomix (a mixture of IL-1β, TNF-α and IFN-γ) significantly enhances TGF-β1-induced EMT in A549 cells as evidenced by acquisition of fibroblast-like cell shape, loss of E-cadherin, and reorganization of F-actin. IL-1β or TNF-α alone can also augment TGF-β1-induced EMT. However, a combination of IL-1β and TNF-α or the cytomix is more potent to induce EMT. Cytomix, but not individual cytokine of IL-1β, TNF-α or IFN-γ, significantly up-regulates expression of TGF-β receptor type I (TβR-I). Suppression of TβR-I, Smad2 or Smad3 by siRNA partially blocks EMT induction by cytomix plus TGF-β1, indicating cytomix augments TGF-β1-induced EMT through enhancing TβR-I and Smad signaling. These results indicate that inflammatory cytokines together with TGF-β1 may play an important role in the development of fibrosis and tumor progress via the mechanism of epithelial-mesenchymal transition.

Original languageEnglish (US)
Pages (from-to)935-944
Number of pages10
JournalCell Motility and the Cytoskeleton
Volume65
Issue number12
DOIs
StatePublished - Dec 1 2008

Fingerprint

Epithelial-Mesenchymal Transition
Cytokines
Interleukin-1
Fibrosis
A549 Cells
Cell Shape
Cadherins
Matrix Metalloproteinases
Small Interfering RNA
Actins
Neoplasms
Intercellular Signaling Peptides and Proteins
Up-Regulation
Cell Culture Techniques
Fibroblasts

Keywords

  • Cancer
  • Cytokine
  • Epithelial-mesenchymal transition
  • Fibrosis

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

Cite this

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abstract = "Epithelial-mesenchymal transition (EMT) is believed to play an important role in fibrosis and tumor invasion. EMT can be induced in vitro cell culture by various stimuli including growth factors and matrix metalloproteinases. In this study, we report that cytomix (a mixture of IL-1β, TNF-α and IFN-γ) significantly enhances TGF-β1-induced EMT in A549 cells as evidenced by acquisition of fibroblast-like cell shape, loss of E-cadherin, and reorganization of F-actin. IL-1β or TNF-α alone can also augment TGF-β1-induced EMT. However, a combination of IL-1β and TNF-α or the cytomix is more potent to induce EMT. Cytomix, but not individual cytokine of IL-1β, TNF-α or IFN-γ, significantly up-regulates expression of TGF-β receptor type I (TβR-I). Suppression of TβR-I, Smad2 or Smad3 by siRNA partially blocks EMT induction by cytomix plus TGF-β1, indicating cytomix augments TGF-β1-induced EMT through enhancing TβR-I and Smad signaling. These results indicate that inflammatory cytokines together with TGF-β1 may play an important role in the development of fibrosis and tumor progress via the mechanism of epithelial-mesenchymal transition.",
keywords = "Cancer, Cytokine, Epithelial-mesenchymal transition, Fibrosis",
author = "Xiang-de Liu",
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N2 - Epithelial-mesenchymal transition (EMT) is believed to play an important role in fibrosis and tumor invasion. EMT can be induced in vitro cell culture by various stimuli including growth factors and matrix metalloproteinases. In this study, we report that cytomix (a mixture of IL-1β, TNF-α and IFN-γ) significantly enhances TGF-β1-induced EMT in A549 cells as evidenced by acquisition of fibroblast-like cell shape, loss of E-cadherin, and reorganization of F-actin. IL-1β or TNF-α alone can also augment TGF-β1-induced EMT. However, a combination of IL-1β and TNF-α or the cytomix is more potent to induce EMT. Cytomix, but not individual cytokine of IL-1β, TNF-α or IFN-γ, significantly up-regulates expression of TGF-β receptor type I (TβR-I). Suppression of TβR-I, Smad2 or Smad3 by siRNA partially blocks EMT induction by cytomix plus TGF-β1, indicating cytomix augments TGF-β1-induced EMT through enhancing TβR-I and Smad signaling. These results indicate that inflammatory cytokines together with TGF-β1 may play an important role in the development of fibrosis and tumor progress via the mechanism of epithelial-mesenchymal transition.

AB - Epithelial-mesenchymal transition (EMT) is believed to play an important role in fibrosis and tumor invasion. EMT can be induced in vitro cell culture by various stimuli including growth factors and matrix metalloproteinases. In this study, we report that cytomix (a mixture of IL-1β, TNF-α and IFN-γ) significantly enhances TGF-β1-induced EMT in A549 cells as evidenced by acquisition of fibroblast-like cell shape, loss of E-cadherin, and reorganization of F-actin. IL-1β or TNF-α alone can also augment TGF-β1-induced EMT. However, a combination of IL-1β and TNF-α or the cytomix is more potent to induce EMT. Cytomix, but not individual cytokine of IL-1β, TNF-α or IFN-γ, significantly up-regulates expression of TGF-β receptor type I (TβR-I). Suppression of TβR-I, Smad2 or Smad3 by siRNA partially blocks EMT induction by cytomix plus TGF-β1, indicating cytomix augments TGF-β1-induced EMT through enhancing TβR-I and Smad signaling. These results indicate that inflammatory cytokines together with TGF-β1 may play an important role in the development of fibrosis and tumor progress via the mechanism of epithelial-mesenchymal transition.

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