Long-term activation of TLR3 by poly(I:C) induces inflammation and impairs lung function in mice.
Long-term activation of TLR3 by poly(I:C) induces inflammation and impairs lung function in mice.
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DOI：
10.1186/1465-9921-10-43
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发表时间：
2009-06-01
影响因子：
5.8
通讯作者：
Das AM
中科院分区：
文献类型：
--
作者：
Stowell NC;Seideman J;Raymond HA;Smalley KA;Lamb RJ;Egenolf DD;Bugelski PJ;Murray LA;Marsters PA;Bunting RA;Flavell RA;Alexopoulou L;San Mateo LR;Griswold DE;Sarisky RT;Mbow ML;Das AM
与感染诱发的哮喘和慢性阻塞性肺病疾病恶化相关的免疫机制尚不完全清楚。 Toll 样受体 (TLR) 3 在识别双链病毒 RNA 中发挥重要作用，从而导致各种炎症介质的产生。因此，对 TLR3 激活的了解应该有助于深入了解病毒引起的肺部疾病恶化的机制。 TLR3 敲除 (KO) 小鼠和 C57B6 (WT) 小鼠经鼻内施用重复剂量的合成双链 RNA 类似物聚 (I:C)。在经聚 (I:C) 处理的小鼠的 BALF 样本中，总细胞数量显着增加，尤其是中性粒细胞。此外，IL-6、CXCL10、JE、KC、mGCSF、CCL3、CCL5 和 TNFα 上调。肺部的组织学分析显示间质中有细胞浸润，小细支气管上皮细胞肥大。与聚（I:C）的促炎作用相关，通过全身体积描记法和气道阻力的侵入性测量来测量，小鼠在基线和对乙酰甲胆碱挑战的反应中均表现出肺功能的显着损害。重要的是，TLR3 KO 小鼠在基线时免受聚 (I:C) 诱导的肺功能变化的影响，这与肺部较轻的炎症相关，并显着减少了上皮细胞肥大。这些发现表明，poly(I:C) 激活 TLR3 可调节肺部局部炎症反应，并表明 TLR3 激活在导致肺功能损伤中发挥着关键作用。因此，TLR3 激活可能是病毒感染导致呼吸道疾病恶化的一种机制。
The immune mechanisms associated with infection-induced disease exacerbations in asthma and COPD are not fully understood. Toll-like receptor (TLR) 3 has an important role in recognition of double-stranded viral RNA, which leads to the production of various inflammatory mediators. Thus, an understanding of TLR3 activation should provide insight into the mechanisms underlying virus-induced exacerbations of pulmonary diseases. TLR3 knock-out (KO) mice and C57B6 (WT) mice were intranasally administered repeated doses of the synthetic double stranded RNA analog poly(I:C). There was a significant increase in total cells, especially neutrophils, in BALF samples from poly(I:C)-treated mice. In addition, IL-6, CXCL10, JE, KC, mGCSF, CCL3, CCL5, and TNFα were up regulated. Histological analyses of the lungs revealed a cellular infiltrate in the interstitium and epithelial cell hypertrophy in small bronchioles. Associated with the pro-inflammatory effects of poly(I:C), the mice exhibited significant impairment of lung function both at baseline and in response to methacholine challenge as measured by whole body plethysmography and an invasive measure of airway resistance. Importantly, TLR3 KO mice were protected from poly(I:C)-induced changes in lung function at baseline, which correlated with milder inflammation in the lung, and significantly reduced epithelial cell hypertrophy. These findings demonstrate that TLR3 activation by poly(I:C) modulates the local inflammatory response in the lung and suggest a critical role of TLR3 activation in driving lung function impairment. Thus, TLR3 activation may be one mechanism through which viral infections contribute toward exacerbation of respiratory disease.
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Toll样受体（TLR）3对病毒诱导的急性肺炎的有害贡献。
影响因子：
6.7
作者：
Le Goffic, Ronan;Balloy, Viviane;Lagranderie, Micheline;Alexopoulou, Lena;Escriou, Nicolas;Flavell, Richard;Chignard, Michel;Si-Tahar, Mustapha
通讯作者：
Si-Tahar, Mustapha
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1073/pnas.0400525101
发表时间：
2004-03-09
影响因子：
11.1
作者：
Tabeta, K;Georgel, P;Beutler, B
通讯作者：
Beutler, B
DOI：
10.1165/rcmb.2003-0388oc
发表时间：
2004-09-01
影响因子：
6.4
作者：
Sha, Q;Truong-Tran, AQ;Schleimer, RP
通讯作者：
Schleimer, RP
DOI：
10.1186/1476-9255-2-16
发表时间：
2005-11-29
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Ritter M;Mennerich D;Weith A;Seither P
通讯作者：
Seither P