Dragon Stéphane, Takhar Manrit Kaur, Shan Lianyu, Hayglass Kent T, Simons F Estelle, Gounni Abdelilah S
Department of Immunology and the CIHR National Training Program in Allergy and Asthma, University of Manitoba, Winnipeg, Mannitoba, Canada.
Biochem Biophys Res Commun. 2009 Jun 26;384(2):167-72. doi: 10.1016/j.bbrc.2009.04.104. Epub 2009 May 3.
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 on 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-9Ralpha 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 macrophage-colony stimulating factor (GM-CSF) up-regulated mRNA and cell surface expression levels of the IL-9Ralpha in primary human and HL-60 differentiated neutrophils. Pharmacological inhibition of NF-kappaB did not affect T(H)2-mediated IL-9Ralpha expression in human neutrophils although IFN-gamma and IL-10 down-regulated IL-9Ralpha 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-9Ralpha expression levels on peripheral blood neutrophils by T(H)2 cytokines.
白细胞介素（IL）-9与哮喘的关键病理特征相关，如气道高反应性、支气管收缩和黏液分泌。IL-9介导的炎症反应依赖于IL-9R的表达，IL-9R已在肺上皮细胞、T淋巴细胞以及最近在气道粒细胞浸润中被报道。在本研究中，我们评估了来自特应性哮喘患者、特应性非哮喘患者和健康正常对照的未分级和纯化的人中性粒细胞中IL-9Rα的调节性和组成性细胞表面表达。我们证明，T(H)2细胞因子（IL-4或IL-13）和粒细胞巨噬细胞集落刺激因子（GM-CSF）上调了原代人中性粒细胞和HL-60分化中性粒细胞中IL-9Rα的mRNA和细胞表面表达水平。NF-κB的药理学抑制并不影响人中性粒细胞中T(H)2介导的IL-9Rα表达，尽管与IL-4、IL-13或GM-CSF共同孵育时，IFN-γ和IL-10下调了IL-9Rα表达。总体而言，我们的结果揭示了IFN-γ和IL-10在调节T(H)2细胞因子对外周血中性粒细胞上可诱导的IL-9Rα表达水平方面的调节功能。
