Interleukin-13 acts as an apoptotic effector on lung epithelial cells and induces pro-fibrotic gene expression in lung fibroblasts
Article first published online: 11 FEB 2008
© 2008 The Authors; Journal compilation © 2008 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 38, Issue 4, pages 619–628, April 2008
How to Cite
Borowski, A., Kuepper, M., Horn, U., Knüpfer, U., Zissel, G., Höhne, K., Luttmann, W., Krause, S., Virchow, J. C. and Friedrich, K. (2008), Interleukin-13 acts as an apoptotic effector on lung epithelial cells and induces pro-fibrotic gene expression in lung fibroblasts. Clinical & Experimental Allergy, 38: 619–628. doi: 10.1111/j.1365-2222.2008.02944.x
- Issue published online: 11 FEB 2008
- Article first published online: 11 FEB 2008
- Submitted 19 March 2007; revised 29 October 2007; accepted 11 December 2007
- IL-13 receptor;
Background IL-13 promotes acute allergic asthma and is discussed to play a role in late asthmatic features such as fibrotic processes and airway remodelling. The contributions of IL-13-mediated mechanisms to subepithelial events related to fibrosis are not yet settled.
Objective We investigated the impact of IL-13 on lung epithelial cells as apoptotic effector and on lung fibroblasts as inducer of pro-fibrotic gene expression.
Methods Using the two lung epithelial cell lines A549 and BEAS-2B as well as primary lung epithelial cells, we investigated the capability of IL-13 to induce apoptosis by both flow-cytometry and ELISA. The ability of IL-13 to increase the expression of pro-fibrotic genes and to exert influence on the expression of its own receptor was investigated by real-time quantitative PCR measurement of mRNAs encoding collagen I, collagen III, basic fibroblast growth factor (bFGF), α-smooth muscle actin (α-SMA) and the IL-13 receptor α1 (IL-13Rα1) chain in human primary lung fibroblasts. The specificity of IL-13-mediated cellular responses was confirmed by means of an inhibitory monoclonal antibody directed to the IL-13 receptor.
Results IL-13 induces apoptosis in lung epithelial cell lines as well as in primary lung epithelial cells. Furthermore, IL-13 increases the expression of mRNA for α-SMA and collagen III, but not for bFGF in human primary lung fibroblasts. The susceptibility of lung fibroblasts to IL-13-induced up-regulation of pro-fibrotic genes is associated with the regulation of IL-13 receptor expression. IL-13-dependent fibrosis-associated effects could be inhibited by antibody-mediated blockade of the IL-13Rα1 subunit.
Conclusion Our findings indicate a function of IL-13 as a mediator in fibrotic processes leading to loss of functional airway tissue in asthma. They also highlight the therapeutic potential of specifically targeting the interaction between IL-13 and its receptor.