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Acta Physiologica 2009; Volume 195, Supplement 669
The 88th Annual Meeting of The German Physiological Society
3/22/2009-3/25/2009
Giessen, Germany
SUNDAY, MARCH 22, AUDIMAX, POSTER AREA CPOSTER SESSIONYOUNG INVESTIGATOR AWARD (POSTER):CELL MOBILIZATION AND CELL SIGNALINGMODERATORS: D. W. RICHTER (GTTINGEN)A. SACHINIDIS (KLN) EFFECT OF TGF-1 AND INFLAMMATORY CYTOKINES ON EMT AND CELL MIGRATION IN ALVEOLAR EPITHELIAL CELLS
Abstract number: YP46
Buckley1 S.T., Medina1 C., Ehrhardt1 C.
1Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland
Rationale: It is thought that the generation of myofibroblasts via epithelial-mesenchymal transition (EMT), a process through which epithelial cells lose their polarity and become motile mesenchymal cells, is a contributory factor in fibrosis. Various growth factors and inflammatory cytokines are purported to orchestrate this process. In this study we assessed the ability of TGF-ß1 and inflammatory cytokines to induce EMT and their effect on cell migration.
Methods:
Alveolar epithelial cells (A549) were stimulated with TGF-ß1 (5 ng/ml) and/or cytomix [IL-1ß + TNF-a + IFN-g] (10 ng/ml). Alterations in cell morphology were assessed using phase contrast microscopy. Changes in expression of EMT markers were measured using immunofluorescence microscopy (IFM). The influence of TGF-ß1, IL-1ß, TNF-a and IFN-g (alone and in combinations) on cell migration was determined using a wound closing assay.
Results:
Control cells exhibited an epithelial morphology with expression of E-cadherin and an absence of a-SMA. Treatment with TGF-ß1 induced EMT with cells adopting a spindle-shaped phenotype. This was coupled with a down regulation of E-cadherin expression and an up-regulation of a-SMA. Cytomix, either alone or in combination with TGF-ß1, was found to induce EMT to a greater extent than TGF-ß1. Cytomix, IL-1ß + TNF-a and IL-1ß alone were all found to significantly (P<0.001) enhance cell migration following wounding. TGF-ß1 had little effect, either alone or when added to different combinations of cytokines.
Conclusions:
These results indicate that inflammatory cytokines together with TGF-ß1 may play an important role in the development of fibrosis via the mechanism of epithelial-mesenchymal transition.
STB is funded by a IRSCET postgraduate scholarship.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 669 :YP46