ISSN:
1365-2222
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveWe wondered whether cetirizine might influence the release of interleukin-8 (IL-8) from human epithelial cells activated with agonists distinct from histamine.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsWe 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 μmol/L) for 30 min and afterwards activated with pro-inflammatory cytokines (TNF-α IL-1β, IL-6, IFN-γ) or different agonists (PMA, NaF, respiratory syncytial virus [RSV]) for 24 h.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsEpithelial cells stimulated with TNF-α IL-1β, 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-α 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-α. Furthermore, a decreased amount of accessible DNA-binding sites of the nuclear factor kappa B (NF-kB) was determined by FACS analysis.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionsThese results suggest that cetirizine reduced the release of IL-8 from A549 cells stimulated with PMA and TNF-α, 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2222.1999.00630.x
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