IL-4 activates equine neutrophils and induces a mixed inflammatory cytokine expression profile with enhanced neutrophil chemotactic mediator release ex vivo
IL-4 activates equine neutrophils and induces a mixed inflammatory cytokine expression profile with enhanced neutrophil chemotactic mediator release ex vivo
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DOI：
10.1152/ajplung.00135.2009
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发表时间：
2010-10-01
影响因子：
4.9
通讯作者：
Lavoie, Jean-Pierre
中科院分区：
文献类型：
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作者：
Lavoie-Lamoureux, Anouk;Moran, Kantuta;Lavoie, Jean-Pierre
Lavoie-Lamoureux A，Moran K，Beauchamp G，Mauel S，施泰因巴赫F，Lefebvre-Lavoie J，Martin JG，Lavoie JP. IL-4激活马中性粒细胞并诱导混合炎性细胞因子表达谱，同时增强中性粒细胞趋化介体离体释放。Am J Physiol Lung Cell Mol Physiol 299：L472-L482，2010.首次发表于2010年7月16日; doi：10.1152/ajplung.00135.2009.-嗜中性粒细胞是过敏性气道炎症中发生的肺病理生理变化的有力贡献者，其通常涉及辅助性T细胞2型（Th 2）细胞因子过表达。我们以前曾报道，马肺内皮细胞被激活的Th 2细胞因子IL-4和表达中性粒细胞的趋化因子刺激后。通过研究重组马IL-4（一种典型的Th 2细胞因子）对从正常动物和患有哮喘气道炎症（马气喘）的马中分离的外周血中性粒细胞（PBN）的影响，我们进一步探索了Th 2驱动的炎症和嗜中性粒细胞相关的可能机制。我们发现，IL-4诱导PBN的形态学变化，IL-8 mRNA的表达的剂量和时间依赖性，以及在培养上清液中的中性粒细胞的趋化因子的释放。此外，IL-4在对照组和哮喘动物的PBN中诱导混合炎症反应，促炎性IL-8和TNF-α表达增加，但IL-1 β明显抑制。IL-4还上调了IL-4 I型受体（IL-4 R α）和CD 23（Fc是RII的一个元件）的表达。重要的是，疾病以及慢性抗原暴露通过PBN修饰基因表达。最后，我们发现用IL-4激活马中性粒细胞涉及STAT 6磷酸化和p38 MAPK和磷脂酰肌醇3-激酶（PI 3 K）;药理学抑制剂SB-203580和LY-294002分别显著逆转IL-4诱导的PBN基因调节。总体而言，本研究的结果增加了马模型中Th 2驱动的炎症和嗜中性粒细胞之间的联系，并进一步扩展了IL-4对中性粒细胞作用的表征。
Lavoie-Lamoureux A, Moran K, Beauchamp G, Mauel S, Steinbach F, Lefebvre-Lavoie J, Martin JG, Lavoie JP. IL-4 activates equine neutrophils and induces a mixed inflammatory cytokine expression profile with enhanced neutrophil chemotactic mediator release ex vivo. Am J Physiol Lung Cell Mol Physiol 299: L472-L482, 2010. First published July 16, 2010; doi:10.1152/ajplung.00135.2009.-Neutrophils are potent contributors to the lung pathophysiological changes occurring in allergic airway inflammation, which typically involve T helper type 2 (Th2) cytokine overexpression. We have previously reported that equine pulmonary endothelial cells are activated by the Th2 cytokine IL-4 and express chemotactic factors for neutrophils after stimulation. We have further explored the possible mechanisms linking Th2-driven inflammation and neutrophilia by studying the effects of recombinant equine IL-4, a prototypical Th2 cytokine, on peripheral blood neutrophils (PBN) isolated from normal animals and from horses with asthmatic airway inflammation (equine heaves). We found that IL-4 induced morphological changes in PBN, dose-and time-dependent expression of IL-8 mRNA, as well as the release of chemotactic factors for neutrophils in culture supernatants. Also, IL-4 induced a mixed inflammatory response in PBN from control and asthmatic-animals with increased expression of proinflammatory IL-8 and TNF-alpha but a marked inhibition of IL-1 beta. IL-4 type I receptor (IL-4R alpha) and CD23 (Fc is an element of RII) expression were also upregulated by IL-4. Importantly, disease as well as chronic antigenic exposure modified gene expression by PBN. Finally, we found that activation of equine neutrophils with IL-4 involved STAT6 phosphorylation and p38 MAPK and phosphatidylinositol 3-kinase (PI3K); the pharmacological inhibitors, SB-203580 and LY-294002, respectively, significantly reversed IL-4-induced gene modulation in PBN. Overall, results from this study add to the link between Th2-driven inflammation and neutrophilia in the equine model and further extend the characterization of IL-4 effects on neutrophils.