The role of interleukin-1 and interleukin-18 in pro-inflammatory and anti-viral responses to rhinovirus in primary bronchial epithelial cells.
The role of interleukin-1 and interleukin-18 in pro-inflammatory and anti-viral responses to rhinovirus in primary bronchial epithelial cells.
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DOI：
10.1371/journal.pone.0063365
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Finch DK
中科院分区：
文献类型：
--
作者：
Piper SC;Ferguson J;Kay L;Parker LC;Sabroe I;Sleeman MA;Briend E;Finch DK
人鼻病毒（HRV）与慢性呼吸道疾病的急性加重有关。在健康个体中，先天性病毒识别途径触发具有直接抗病毒活性的分子和促炎介质的释放，所述促炎介质募集免疫细胞以支持病毒清除。白细胞介素-1 α（IL-1α）、白细胞介素-1 β（IL-1β）和白细胞介素-18（IL-18）在嗜中性粒细胞炎症的形成中起关键作用，嗜中性粒细胞炎症常见于气道病毒感染，被认为对呼吸道疾病有害。因此，我们研究了这些分子在HRV感染原代人上皮细胞中的作用。我们发现所有三种细胞因子都从感染的上皮细胞释放。这些细胞因子的释放不依赖于细胞死亡，只有IL-1β和IL-18的释放依赖于caspase-1的催化活性。阻断IL-1而非IL-18信号传导抑制促炎介质和中性粒细胞趋化因子的上调，但对病毒诱导的干扰素和干扰素诱导基因的产生没有影响，在mRNA和蛋白质水平上测量。在有和没有IL-1 RI阻断的情况下检测到相似的病毒mRNA水平。因此，病毒识别下游的IL-1信号传导（可能涉及IL-1β和IL-1α）在诱导促炎信号中起关键作用，并可能在免疫细胞响应上皮细胞引发的病毒感染的募集和活化中起关键作用，同时不参与直接的抗病毒应答。
Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1α), interleukin-1beta (IL-1β) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1β and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1β and IL-1α, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses.
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影响因子：
82.9
作者：
Chen, Chun-Jen;Kono, Hajime;Rock, Kenneth L.
通讯作者：
Rock, Kenneth L.
影响因子：
24.3
作者：
Seemungal, TAR;Harper-Owen, R;Wedzicha, JA
通讯作者：
Wedzicha, JA
影响因子：
4.4
作者：
Leung, BP;Culshaw, S;McInnes, IB
通讯作者：
McInnes, IB
DOI：
10.1513/pats.200504-025sr
发表时间：
2005-01-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Mallia, Patrick;Johnston, Sebastian L
通讯作者：
Johnston, Sebastian L
影响因子：
3.8
作者：
Manigold, T;Bocker, U;Rossol, S
通讯作者：
Rossol, S