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-1beta, TNF-alpha and IFN-gamma) 
significantly enhances TGF-beta1-induced EMT in A549 cells as evidenced by 
acquisition of fibroblast-like cell shape, loss of E-cadherin, and 
reorganization of F-actin. IL-1beta or TNF-alpha alone can also augment 
TGF-beta1-induced EMT. However, a combination of IL-1beta and TNF-alpha or the 
cytomix is more potent to induce EMT. Cytomix, but not individual cytokine of 
IL-1beta, TNF-alpha or IFN-gamma, significantly up-regulates expression of 
TGF-beta receptor type I (TbetaR-I). Suppression of TbetaR-I, Smad2 or Smad3 by 
siRNA partially blocks EMT induction by cytomix plus TGF-beta1, indicating 
cytomix augments TGF-beta1-induced EMT through enhancing TbetaR-I and Smad 
signaling. These results indicate that inflammatory cytokines together with 
TGF-beta1 may play an important role in the development of fibrosis and tumor 
progress via the mechanism of epithelial-mesenchymal transition.