Impact of cigarette smoke exposure on innate immunity: a Caenorhabditis elegans model.
Impact of cigarette smoke exposure on innate immunity: a Caenorhabditis elegans model.
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DOI：
10.1371/journal.pone.0006860
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发表时间：
2009-08-31
期刊：
影响因子：
3.7
通讯作者：
Chu HW
中科院分区：
文献类型：
--
作者：
Green RM;Gally F;Keeney JG;Alper S;Gao B;Han M;Martin RJ;Weinberger AR;Case SR;Minor MN;Chu HW
吸烟是慢性阻塞性肺疾病（COPD）和肺癌的主要原因。呼吸道细菌感染已被证明参与COPD的发展，沿着气道先天免疫受损。为了解决香烟烟雾（CS）对宿主先天防御机制的体内影响，我们利用秀丽隐杆线虫（C. elegans），具有先天免疫系统，但缺乏适应性免疫功能。铜绿假单胞菌（PA）从C. CS抑制了elegans的生长微阵列分析确定了6个候选基因，CS暴露后减少2倍或更多，具有人类直系同源物，并可能参与先天免疫。为了证实CS下调基因在对PA的先天免疫应答中的作用，在C. elegans以抑制感兴趣的基因，随后PA感染以确定该基因是否影响先天免疫。抑制编码脂质结合蛋白的lbp-7导致肠PA水平增加。原代人支气管上皮细胞显示表达人脂肪酸结合蛋白5（FABP-5）（lpb-7的人直向同源物）的mRNA。有趣的是，患有COPD的人类吸烟者的FABP-5 mRNA水平显著低于（p = 0.036）来自不患有COPD的吸烟者的FABP-5 mRNA水平。 此外，FABP-5 mRNA水平在细菌（即，原代人支气管上皮细胞培养（气-液界面培养）中肺炎支原体）感染。我们的研究结果表明，C。线虫模型提供了一种新的体内方法来专门研究暴露于香烟烟雾导致的先天性免疫缺陷，线虫的结果可能提供对人类气道上皮细胞生物学和香烟烟雾暴露的深入了解。
Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD) and lung cancer. Respiratory bacterial infections have been shown to be involved in the development of COPD along with impaired airway innate immunity. To address the in vivo impact of cigarette smoke (CS) exclusively on host innate defense mechanisms, we took advantage of Caenorhabditis elegans (C. elegans), which has an innate immune system but lacks adaptive immune function. Pseudomonas aeruginosa (PA) clearance from intestines of C. elegans was dampened by CS. Microarray analysis identified 6 candidate genes with a 2-fold or greater reduction after CS exposure, that have a human orthologue, and that may participate in innate immunity. To confirm a role of CS-down-regulated genes in the innate immune response to PA, RNA interference (RNAi) by feeding was carried out in C. elegans to inhibit the gene of interest, followed by PA infection to determine if the gene affected innate immunity. Inhibition of lbp-7, which encodes a lipid binding protein, resulted in increased levels of intestinal PA. Primary human bronchial epithelial cells were shown to express mRNA of human Fatty Acid Binding Protein 5 (FABP-5), the human orthologue of lpb-7. Interestingly, FABP-5 mRNA levels from human smokers with COPD were significantly lower (p = 0.036) than those from smokers without COPD. Furthermore, FABP-5 mRNA levels were up-regulated (7-fold) after bacterial (i.e., Mycoplasma pneumoniae) infection in primary human bronchial epithelial cell culture (air-liquid interface culture). Our results suggest that the C. elegans model offers a novel in vivo approach to specifically study innate immune deficiencies resulting from exposure to cigarette smoke, and that results from the nematode may provide insight into human airway epithelial cell biology and cigarette smoke exposure.
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DOI：
10.1073/pnas.96.2.715
发表时间：
1999-01-19
影响因子：
11.1
作者：
Tan, MW;Mahajan-Miklos, S;Ausubel, FM
通讯作者：
Ausubel, FM
影响因子：
6
作者：
Chu, HW;Balzar, S;Wenzel, SE
通讯作者：
Wenzel, SE
影响因子：
12.3
作者：
通讯作者：
--
影响因子：
56.9
作者：
Kim, DH;Feinbaum, R;Ausubel, FM
通讯作者：
Ausubel, FM
DOI：
10.1073/pnas.0604055103
发表时间：
2006-07-05
影响因子：
11.1
作者：
Moy, Terence I.;Ball, Anthony R.;Ausubel, Frederick M.
通讯作者：
Ausubel, Frederick M.