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 susceptib ility to asthma. These data are supported by the finding that allergen-expo sed IL-9-transgenic mice exhibit many features that are characteristic of h uman asthma (airway eosinophilia, elevated serum IgE and bronchial hyperres ponsiveness) as compared to the background strain. A striking feature of th ese animals is a robust peribronchial and perivascular eosinophilia after a llergen challenge, suggesting that IL-9 is a potent factor in regulating th is process. In an attempt to gain insights into the molecular mechanism gov erning IL-9 modulation of lung eosinophilia, we investigated the ability of this cytokine to induce the expression of CC-type chemokines in the lung b ecause of their effect on stimulating eosinophil chemotaxis. Here we show t hat IL-9-transgenic mice in contrast to their congenic controls exhibit bas eline lung eosinophilia that is associated with the up-regulation of CC-che mokine 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 epithel ial cultures and cell lines induced the expression of these chemokines in v itro. These data support a mechanism for IL-9 in regulating the expression of eosinophil chemotactic factors in lung epithelial cells.