Rhinovirus C15 Induces Airway Hyperresponsiveness via Calcium Mobilization in Airway Smooth Muscle
Rhinovirus C15 Induces Airway Hyperresponsiveness via Calcium Mobilization in Airway Smooth Muscle
复制标题
鼻病毒C15通过气道平滑肌钙动员诱导气道高反应性
DOI：
10.1165/rcmb.2019-0004oc
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发表时间：
2020-03-01
影响因子：
6.4
通讯作者：
Koziol-White, Cynthia J.
中科院分区：
文献类型：
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作者：
Parikh, Vishal;Scala, Jacqueline;Koziol-White, Cynthia J.
鼻病毒(RV)暴露会引起哮喘的加重，这对全世界的发病率和死亡率都有显著影响。RV诱导气道高反应性(AHR)的机制或特定RV血清型差异地引起AHR的机制仍不清楚。我们推测RV感染可引起AHR和炎症介质的释放，这与RV感染的程度有关。此外，我们假设鼻病毒C诱导的AHR需要从上皮细胞释放旁分泌或自分泌介质，以调节激动剂诱导的人气道平滑肌钙动员。在这些研究中，我们使用体外模型来测量人类精密切割肺切片中受感染的呼吸道的支气管收缩和介质释放，以了解RV暴露如何改变呼吸道收缩。我们发现，鼻病毒C15(RV-C15)感染增加了卡巴胆碱诱导的气道狭窄，并显著增加了IP-10(干扰素-γ诱导蛋白10)和MIP-1β(巨噬细胞炎性蛋白-1β)的释放，但不增加IL-6。RV-C15感染人呼吸道上皮细胞可增加激动剂诱导的细胞内钙流量和肌球蛋白轻链对氨甲胆碱的磷酸化，但不能在组胺刺激后增加。我们的数据表明，RV-C15诱导的结构细胞炎症反应与病毒载量有关，但炎症反应和激动剂介导的人类小气道收缩的变化与组织的病毒载量无关。
Rhinovirus (RV) exposure evokes exacerbations of asthma that markedly impact morbidity and mortality worldwide. The mechanisms by which RV induces airway hyperresponsiveness (AHR) or by which specific RV serotypes differentially evoke AHR remain unknown. We posit that RV infection evokes AHR and inflammatory mediator release, which correlate with degrees of RV infection. Furthermore, we posit that rhinovirus C-induced AHR requires paracrine or autocrine mediator release from epithelium that modulates agonist-induced calcium mobilization in human airway smooth muscle. In these studies, we used an ex vivo model to measure bronchoconstriction and mediator release from infected airways in human precision cut lung slices to understand how RV exposure alters airway constriction. We found that rhinovirus C15 (RV-C15) infection augmented carbachol-induced airway narrowing and significantly increased release of IP-10 (IFN-gamma-induced protein 10) and MIP-1 beta (macrophage inflammatory protein-1 beta) but not IL-6. RV-C15 infection of human airway epithelial cells augmented agonist-induced intracellular calcium flux and phosphorylation of myosin light chain in co-cultured human airway smooth muscle to carbachol, but not after histamine stimulation. Our data suggest that RV-C15-induced structural cell inflammatory responses are associated with viral load but that inflammatory responses and alterations in agonist-mediated constriction of human small airways are uncoupled from viral load of the tissue.