title: Cetirizine counter-regulates interleukin-8 release from human epithelial cells (A549)
abstract: BACKGROUND
  Cetirizine, a H1-receptor antagonist, exerts besides its well-known anti-allergic potential an array of anti-inflammatory activities. In particular epithelial cells activated in the presence of cetirizine showed a reduced ICAM-1 cell surface expression and a diminished release of sICAM-1.
  
  
  OBJECTIVE
  We wondered whether cetirizine might influence the release of interleukin-8 (IL-8) from human epithelial cells activated with agonists distinct from histamine.
  
  
  METHODS
  We used the human lung epithelial cell line A549 for our in vitro studies. IL-8 release was determined by IL-8 enzyme immunoassay, the intracellular staining for IL-8 and NF-kB was analysed by FACS analysis and IL-8 mRNA steady state level was studied by Northern blot analysis. Confluent epithelial cell monolayer were pre-incubated with cetirizine (0.01 -1.0 micromol/L) for 30 min and afterwards activated with pro-inflammatory cytokines (TNF-alpha IL-1beta, IL-6, IFN-gamma) or different agonists (PMA, NaF, respiratory syncytial virus [RSV]) for 24 h.
  
  
  RESULTS
  Epithelial cells stimulated with TNF-alpha IL-1beta, PMA and RSV, respectively, showed a significantly increased release of IL-8. Pre-incubation with cetirizine diminished the IL-8 release from cells activated with TNF-alpha or PMA in a significant manner. The reduced IL-8 release coincided with a diminished percentage of cells expressing IL-8. Northern blot analysis revealed a reduced steady state level of IL-8 mRNA in cells pretreated with cetirizine and stimulated with TNF-alpha. Furthermore, a decreased amount of accessible DNA-binding sites of the nuclear factor kappa B (NF-kB) was determined by FACS analysis.
  
  
  CONCLUSIONS
  These results suggest that cetirizine reduced the release of IL-8 from A549 cells stimulated with PMA and TNF-alpha, respectively, by lowering IL-8 gene expression. Therefore, cetirizine might exert anti-inflammatory effects beyond its H1-receptor antagonistic activity in the course of inflammatory respiratory tract disorders such as bronchial asthma and allergic rhinitis.
authors.affiliation: Institute of Medical Microbiology and Immunology, AG Infektabwehr, Ruhr-University, Bochum, Germany; Institute of Medical Immunology, Charité-Campus Mitte, Humboldt University, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Arnold
authors.forename: J
authors.initials: J
authors.lastname: Rihoux
authors.forename: W
authors.initials: W
authors.lastname: König
mesh_terms: D015152:Blotting, Northern; D017332:Cetirizine / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology; D005434:Flow Cytometry; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D012969:Sodium Fluoride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D006634:Histamine H1 Antagonists; D016209:Interleukin-8; D012969:Sodium Fluoride; D013755:Tetradecanoylphorbol Acetate; D017332:Cetirizine