在小儿支气管上皮细胞模型中，Th2细胞因子增强了鼻病毒16型诱导的IP-10和IL-8释放。
Rhinovirus-16 induced release of IP-10 and IL-8 is augmented by Th2 cytokines in a pediatric bronchial epithelial cell model.
作者信息
Cakebread Julie A, Haitchi Hans Michael, Xu Yunhe, Holgate Stephen T, Roberts Graham, Davies Donna E
机构信息
Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom.
Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom; NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom.
出版信息
PLoS One. 2014 Apr 4;9(4):e94010. doi: 10.1371/journal.pone.0094010. eCollection 2014.
BACKGROUND
In response to viral infection, bronchial epithelial cells increase inflammatory cytokine release to activate the immune response and curtail viral replication. In atopic asthma, enhanced expression of Th2 cytokines is observed and we postulated that Th2 cytokines may augment the effects of rhinovirus-induced inflammation.
METHODS
Primary bronchial epithelial cell cultures from pediatric subjects were treated with Th2 cytokines for 24 h before infection with RV16. Release of IL-8, IP-10 and GM-CSF was measured by ELISA. Infection was quantified using RTqPCR and TCID50. Phosphatidyl inositol 3-kinase (PI3K) and P38 mitogen activated protein kinase (MAPK) inhibitors and dexamethasone were used to investigate differences in signaling pathways.
RESULTS
The presence of Th2 cytokines did not affect RV replication or viral titre, yet there was a synergistic increase in IP-10 release from virally infected cells in the presence of Th2 cytokines. Release of IL-8 and GM-CSF was also augmented. IP-10 release was blocked by a PI3K inhibitor and IL-8 by dexamethasone.
CONCLUSION
Th2 cytokines increase release of inflammatory cytokines in the presence of rhinovirus infection. This increase is independent of effects of virus replication. Inhibition of the PI3K pathway inhibits IP-10 expression.
背景
作为对病毒感染的反应，支气管上皮细胞会增加炎性细胞因子的释放，以激活免疫反应并抑制病毒复制。在特应性哮喘中，观察到Th2细胞因子的表达增强，我们推测Th2细胞因子可能会增强鼻病毒诱导的炎症反应。
方法
来自儿科受试者的原代支气管上皮细胞培养物在感染RV16之前用Th2细胞因子处理24小时。通过酶联免疫吸附测定法测量白细胞介素-8（IL-8）、γ干扰素诱导蛋白10（IP-10）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的释放。使用逆转录定量聚合酶链反应（RTqPCR）和半数组织培养感染剂量（TCID50）对感染进行定量。使用磷脂酰肌醇3激酶（PI3K）和p38丝裂原活化蛋白激酶（MAPK）抑制剂以及地塞米松来研究信号通路的差异。
结果
Th2细胞因子的存在不影响RV复制或病毒滴度，但在存在Th2细胞因子的情况下，病毒感染细胞释放的IP-10有协同增加。IL-8和GM-CSF的释放也增加。IP-10的释放被PI3K抑制剂阻断，IL-8的释放被地塞米松阻断。
结论
在鼻病毒感染的情况下，Th2细胞因子会增加炎性细胞因子的释放。这种增加与病毒复制的影响无关。PI3K途径的抑制会抑制IP-10的表达。
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