Oral feeding with probiotic Lactobacillus rhamnosus attenuates cigarette smoke-induced COPD in C57Bl/6 mice: Relevance to inflammatory markers in human bronchial epithelial cells
Oral feeding with probiotic Lactobacillus rhamnosus attenuates cigarette smoke-induced COPD in C57Bl/6 mice: Relevance to inflammatory markers in human bronchial epithelial cells
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DOI：
10.1371/journal.pone.0225560
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发表时间：
2020-04-24
期刊：
影响因子：
3.7
通讯作者：
Aimbire, F.
中科院分区：
文献类型：
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作者：
Carvalho, J. L.;Miranda, M.;Aimbire, F.
COPD是一种流行的肺部疾病，对公众健康有重大影响。受影响的气道表现出肺嗜中性粒细胞和随后的促炎性细胞因子和蛋白酶的分泌，这导致肺气肿。益生菌作为先天免疫系统的非特异性调节剂，可改善多种炎症反应。为了研究鼠李糖乳杆菌（Lr）对香烟烟雾（CS）诱导的COPD的影响，在COPD诱导前一周期间用Lr处理C57 B1/6小鼠，并且每周三次直至安乐死。对于体外测定，在添加CSE之前1小时用Lr处理在24小时期间暴露于香烟烟雾提取物的鼠支气管上皮细胞以及人支气管上皮细胞。激光治疗减弱了气道和肺实质的炎症反应，减少了炎症细胞浸润和促炎细胞因子和趋化因子的产生。此外，LR治疗的小鼠在肺组织和肺重塑中表现出较低的金属蛋白酶。与肺组织中TLR 2、TLR 4、TLR 9、STAT 3和NF-κ B的表达减少平行，Lr增加IL-10以及SOCS 3和TIMP 1/2的水平，表明抗炎环境的诱导。类似地，暴露于CSE的鼠支气管上皮细胞以及人支气管上皮细胞（BEAS）产生促炎细胞因子和趋化因子，其被与抗炎分子的产生相关的Lr处理抑制。此外，Lr的存在还调节COPD小鼠组BALF中发现的COPD相关转录的表达，即，Lr下调NF-κ B和STAT 3的表达，并反向上调SOCS 3的表达。因此，我们的研究结果表明，Lr在CS暴露后调节人支气管上皮细胞中促炎细胞因子和抗炎细胞因子之间的平衡，它可以成为改善与COPD相关的肺部炎症反应的有用工具。
COPD is a prevalent lung disease with significant impacts on public health. Affected airways exhibit pulmonary neutrophilia and consequent secretion of pro-inflammatory wcytokines and proteases, which result in lung emphysema. Probiotics act as nonspecific modulators of the innate immune system that improve several inflammatory responses. To investigate the effect of Lactobacillus rhamnosus (Lr) on cigarette smoke (CS)-induced COPD C57Bl/6 mice were treated with Lr during the week before COPD induction and three times/week until euthanasia. For in vitro assays, murine bronchial epithelial cells as well as human bronchial epithelial cells exposed to cigarette smoke extract during 24 hours were treated with Lr 1 hour before CSE addition. Lr treatment attenuated the inflammatory response both in the airways and lung parenchyma, reducing inflammatory cells infiltration and the production of pro-inflammatory cytokines and chemokines. Also, Lr-treated mice presented with lower metalloproteases in lung tissue and lung remodeling. In parallel to the reduction in the expression of TLR2, TLR4, TLR9, STAT3, and NF-kappa B in lung tissue, Lr increased the levels of IL-10 as well as SOCS3 and TIMP1/2, indicating the induction of an anti-inflammatory environment. Similarly, murine bronchial epithelial cells as well as human bronchial epithelial cells (BEAS) exposed to CSE produced pro-inflammatory cytokines and chemokines, which were inhibited by Lr treatment in association with the production of anti-inflammatory molecules. Moreover, the presence of Lr also modulated the expression of COPD-associated transcription found into BALF of COPD mice group, i.e., Lr downregulated expression of NF-kappa B and STAT3, and inversely upregulated increased expression of SOCS3. Thus, our findings indicate that Lr modulates the balance between pro- and anti-inflammatory cytokines in human bronchial epithelial cells upon CS exposure and it can be a useful tool to improve the lung inflammatory response associated with COPD.