title: Interleukin-33 exacerbates allergic bronchoconstriction in the mice via activation of mast cells.
abstract: BACKGROUND
  Interleukin-33 (IL-33) is implicated as an epithelium-derived danger signal promoting Th2-dependent responses in asthma. We hypothesized that IL-33 might also have direct effects on mast cell-driven allergic airway obstruction.
  
  
  METHODS
  The effects of IL-33 on allergic responses in the airways of sensitized mice were assessed both in vivo and ex vivo, as well as on cultured mast cells in vitro.
  
  
  RESULTS
  In vivo, the allergen-induced increase in resistance in the conducting airways was enhanced in mice pretreated with IL-33. Also, in the isolated airways, the allergen-induced contractions were increased in preparations from animals subjected to intranasal IL-33 pretreatment. These effects in vivo and ex vivo were blocked by the 5-HT2A receptor antagonist ketanserin and absent in mice without mast cells. Likewise, the IL-33-induced enhancement of the allergen response was absent in isolated airways from mice lacking the IL-33 receptor. Moreover, exposure to IL-33 increased secretion of serotonin from allergen-challenged isolated airways. In cultured mast cells, IL-33 enhanced the expression of tryptophan hydroxylase 1, serotonin synthesis, and storage, as well as the secretion of serotonin following IgE receptor cross-linking.
  
  
  CONCLUSIONS
  These results demonstrate that IL-33 exacerbates allergic bronchoconstriction by increasing synthesis, storage, and secretion of serotonin from the mast cell. This mechanism has implications for the development of airway obstruction in asthma.
authors: Unit of Experimental Asthma and Allergy Research, Institute of Environmental Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: L C
authors: LC
authors: Sjöberg
authors: J A
authors: JA
authors: Gregory
authors: S-E
authors: SE
authors: Dahlén
authors: G P
authors: GP
authors: Nilsson
authors: M
authors: M
authors: Adner
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D016084:Bronchoconstriction / Q000276:immunology*; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology; D000067596:Interleukin-33 / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D060888:Real-Time Polymerase Chain Reaction; D012701:Serotonin / Q000276:immunology / Q000378:metabolism
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D012701:Serotonin
keywords: asthma; early allergic reaction; exacerbations; interleukin-33; serotonin