title: Interleukin-13 acts as an apoptotic effector on lung epithelial cells and induces pro-fibrotic gene expression in lung fibroblasts.
abstract: 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), alpha-smooth muscle actin (alpha-SMA) and the IL-13 receptor alpha1 (IL-13Ralpha1) 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 alpha-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-13Ralpha1 subunit.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, University of Jena Medical School, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Borowski
authors.forename: M
authors.initials: M
authors.lastname: Kuepper
authors.forename: U
authors.initials: U
authors.lastname: Horn
authors.forename: U
authors.initials: U
authors.lastname: Knüpfer
authors.forename: G
authors.initials: G
authors.lastname: Zissel
authors.forename: K
authors.initials: K
authors.lastname: Höhne
authors.forename: W
authors.initials: W
authors.lastname: Luttmann
authors.forename: S
authors.initials: S
authors.lastname: Krause
authors.forename: J C
authors.initials: JC
authors.lastname: Virchow
authors.forename: K
authors.initials: K
authors.lastname: Friedrich
mesh_terms: D000199:Actins / Q000187:drug effects / Q000235:genetics; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D024061:Collagen Type III / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D053660:Receptors, Interleukin-13 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D024061:Collagen Type III; D018793:Interleukin-13; D012333:RNA, Messenger; D053660:Receptors, Interleukin-13; D015847:Interleukin-4