TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema
TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema
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DOI：
10.1152/ajplung.00102.2012
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发表时间：
2012-11-01
影响因子：
4.9
通讯作者：
Choi, Augustine M. K.
中科院分区：
文献类型：
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作者：
An, Chang Hyeok;Wang, Xiao Mei;Choi, Augustine M. K.
安昌，王晓明，林慧聪，Ifedigbo E, Washko GR, Ryter SW, Choi AMK。TLR4缺乏促进香烟引起的肺气肿的自噬。[J] .中国生物医学工程学报，2016,31(4):559 - 567。首次发表于2012年9月13日；doi: 10.1152 / ajplung.00102.2012。toll样受体（TLRs）在肺内稳态中发挥重要的非免疫功能。TLR4缺乏促进肺气肿。我们研究了TLR4在调节香烟烟雾（CS）诱导的自噬、细胞凋亡和肺气肿中的作用。肺组织取自慢性阻塞性肺疾病（COPD）患者。将C3H/HeJ （tlr4突变）小鼠和C57BL/10ScNJ （tlr4缺陷）小鼠及其对照品系暴露于慢性CS或空气中。将人或小鼠上皮细胞（野生型、tlr4敲低型和tlr4缺陷型）暴露于cs提取物（CSE）中。通过Western blot或共聚焦成像分析样品的TLR4表达、自噬或凋亡蛋白。慢性阻塞性肺疾病肺组织和暴露于CSE的人肺上皮细胞显示TLR4表达增加，自噬[微管相关蛋白-1轻链- 3b (LC3B)]和凋亡（cleaved caspase-3）标志物增加。转染TLR4 siRNA的Beas-2B细胞与对照细胞相比，在暴露于CSE后，LC3B的表达增加。tlr4缺陷小鼠肺泡II型细胞中LC3B和裂解型caspase-3的基础表达和cse诱导表达均升高。慢性cs暴露的野生型小鼠出现空域扩大；然而，在cs暴露后，tlr4突变或tlr4缺陷小鼠的空域相对于野生型小鼠明显增加。tlr4突变或tlr4缺陷小鼠在基础条件下和CS暴露后LC3B水平较高。在暴露于CS的tlr4缺陷小鼠中，cleaved caspase-3的表达明显增加。我们描述了TLR4在CS反应中对肺肺气肿变化的保护性调节功能。
An CH, Wang XM, Lam HC, Ifedigbo E, Washko GR, Ryter SW, Choi AMK. TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema. Am J Physiol Lung Cell Mol Physiol 303: L748-L757, 2012. First published September 13, 2012; doi:10.1152/ajplung.00102.2012.-Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.