Interleukin (IL)-9 is associated with key pathological features of asthma such as airway hyperresponsiveness, bronchoconstriction and mucus production. Inflammatory responses mediated by IL-9 rely oil the expression of the IL-9R which has been reported on lung epithelial cells, T lymphocytes and recently on airway granulocyte infiltrates. In this study, we assessed the regulatory and constitutive cell surface expression of the IL-9R alpha in unfractionated and purified human neutrophils from atopic asthmatics, atopic non-asthmatics and healthy normal controls. We demonstrate that T(H)2 cytokines (IL-4 or IL-13) and granulocyte rnacrophage-colony stimulating factor (GM-CSF) up-regulated mRNA and cell surface expression levels of the IL-9R alpha in primary human and HL-60 differentiated neutrophils. Pharmacological inhibition of NF-kappa B did not affect T(H)2-mediated IL-9R alpha expression in human neutrophils although IFN-gamma and IL-10 down-regulated IL-9R alpha expression when co-incubated with IL-4, IL-13 or GM-CSF. Collectively, our results reveal a regulatory function for IFN-gamma and IL-10 on modulating the inducible IL-9R alpha. expression levels on peripheral blood neutrophils by T(H)2 cytokines. (C) 2009 Elsevier Inc. All rights reserved.