IL-9 induces chemokine expression in lung epithelial cells and baseline airway eosinophilia in transgenic mice.
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.
Dong
Q
Q
Magainin Institute of Molecular Medicine, Magainin Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA.
Louahed
J
J
Vink
A
A
Sullivan
C D
CD
Messler
C J
CJ
Zhou
Y
Y
Haczku
A
A
Huaux
F
F
Arras
M
M
Holroyd
K J
KJ
Renauld
J C
JC
Levitt
R C
RC
Nicolaides
N C
NC
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
D000485:Allergens; D018925:Chemokines; D017931:DNA Primers; D016906:Interleukin-9