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Keywords:

  • apoptosis;
  • asthma;
  • fibrosis;
  • IL-13 receptor;
  • IL-13

Summary

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.