title: IL-9 induces chemokine expression in lung epithelial cells and baseline airway eosinophilia in transgenic mice.
abstract: Recent data have identified IL-9 as a key cytokine in determining susceptibility to asthma. These data are supported by the finding that allergen-exposed IL-9-transgenic mice exhibit many features that are characteristic of human asthma (airway eosinophilia, elevated serum IgE and bronchial hyperresponsiveness) as compared to the background strain. A striking feature of these animals is a robust peribronchial and perivascular eosinophilia after allergen challenge, suggesting that IL-9 is a potent factor in regulating this process. In an attempt to gain insights into the molecular mechanism governing IL-9 modulation of lung eosinophilia, we investigated the ability of this cytokine to induce the expression of CC-type chemokines in the lung because of their effect on stimulating eosinophil chemotaxis. Here we show that IL-9-transgenic mice in contrast to their congenic controls exhibit baseline lung eosinophilia that is associated with the up-regulation of CC-chemokine expression in the airway. This effect appears to be through a direct action of IL-9 because the addition of recombinant IL-9 to primary epithelial cultures and cell lines induced the expression of these chemokines in vitro. These data support a mechanism for IL-9 in regulating the expression of eosinophil chemotactic factors in lung epithelial cells.
authors.affiliation: Magainin Institute of Molecular Medicine, Magainin Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Dong
authors.forename: J
authors.initials: J
authors.lastname: Louahed
authors.forename: A
authors.initials: A
authors.lastname: Vink
authors.forename: C D
authors.initials: CD
authors.lastname: Sullivan
authors.forename: C J
authors.initials: CJ
authors.lastname: Messler
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: A
authors.initials: A
authors.lastname: Haczku
authors.forename: F
authors.initials: F
authors.lastname: Huaux
authors.forename: M
authors.initials: M
authors.lastname: Arras
authors.forename: K J
authors.initials: KJ
authors.lastname: Holroyd
authors.forename: J C
authors.initials: JC
authors.lastname: Renauld
authors.forename: R C
authors.initials: RC
authors.lastname: Levitt
authors.forename: N C
authors.initials: NC
authors.lastname: Nicolaides
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte; D017931:DNA Primers / Q000235:genetics; D004802:Eosinophilia / Q000209:etiology* / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D016906:Interleukin-9 / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015854:Up-Regulation
chemical_list: D000485:Allergens; D018925:Chemokines; D017931:DNA Primers; D016906:Interleukin-9