Macrophages Inhibit Ciliary Protein Levels by Secreting BMP-2 Leading to Airway Epithelial Remodeling Under Cigarette Smoke Exposure.
Macrophages Inhibit Ciliary Protein Levels by Secreting BMP-2 Leading to Airway Epithelial Remodeling Under Cigarette Smoke Exposure.
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巨噬细胞通过分泌 BMP-2 抑制纤毛蛋白水平，导致香烟烟雾暴露下的气道上皮重塑
DOI：
10.3389/fmolb.2021.663987
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发表时间：
2021
影响因子：
5
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Wang Z;Liang W;Ma C;Wang J;Gao X;Wei L
慢性阻塞性肺疾病(COPD)是世界范围内发病率和死亡率均较高的慢性呼吸系统疾病。到目前为止，吸烟仍然是其主要原因。慢性阻塞性肺疾病的特点是肺气肿和气道重塑，以及以巨噬细胞为主的慢性炎症。已有研究报道巨噬细胞参与肺气肿和慢性炎症，但是否存在气道重塑和巨噬细胞之间的联系尚不清楚。在这项研究中，我们发现，急性和慢性香烟烟雾暴露导致小鼠模型肺内巨噬细胞增加，呼吸道上皮纤毛细胞减少。体外实验结果表明，与人巨噬细胞系THP-1共培养可抑制BEAS-2B细胞纤毛蛋白(β-微管蛋白-IV)的表达，且这种抑制作用随香烟烟雾提取物的刺激而增强。根据转录组测序的结果，我们重点研究了巨噬细胞分泌的可能介导这种抑制作用的蛋白质-骨形态发生蛋白-2(BMP-2)。进一步的研究证实，BMP-2蛋白抑制了CSE刺激下BEAS-2B细胞的β-微管蛋白-IV蛋白水平。巧合的是，这种抑制作用几乎可以被BMP受体抑制剂LDN阻断，或者可以被BMP-2 siRNA干扰。本研究提示，烟雾暴露引起肺内巨噬细胞的活化和浸润，导致BMP-2的高表达，进而抑制支气管上皮细胞纤毛蛋白水平，促进呼吸道上皮细胞重塑，加重COPD的发生发展。
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high morbidity and mortality worldwide. So far, smoking is still its leading cause. The characteristics of COPD are emphysema and airway remodeling, as well as chronic inflammation, which were predominated by macrophages. Some studies have reported that macrophages were involved in emphysema and chronic inflammation, but whether there is a link between airway remodeling and macrophages remains unclear. In this study, we found that both acute and chronic cigarette smoke exposure led to an increase of macrophages in the lung and a decrease of ciliated cells in the airway epithelium of a mouse model. The results of in vitro experiments showed that the ciliary protein (β-tubulin-IV) levels of BEAS-2B cells could be inhibited when co-cultured with human macrophage line THP-1, and the inhibitory effect was augmented with the stimulation of cigarette smoke extract (CSE). Based on the results of transcriptome sequencing, we focused on the protein, bone morphogenetic protein-2 (BMP-2), secreted by the macrophage, which might mediate this inhibitory effect. Further studies confirmed that BMP-2 protein inhibited β-tubulin-IV protein levels of BEAS-2B cells under the stimulation of CSE. Coincidentally, this inhibitory effect could be nearly blocked by the BMP receptor inhibitor, LDN, or could be interfered with BMP-2 siRNA. This study suggests that activation and infiltration of macrophages in the lung induced by smoke exposure lead to a high expression of BMP-2, which in turn inhibits the ciliary protein levels of the bronchial epithelial cells, contributing to the remodeling of airway epithelium, and aggravates the development of COPD.
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影响因子：
9
作者：
Caramori G;Casolari P;Barczyk A;Durham AL;Di Stefano A;Adcock I
通讯作者：
Adcock I
影响因子：
6
作者：
De Cunto, Giovanna;Lunghi, Benedetta;Lucattelli, Monica
通讯作者：
Lucattelli, Monica
DOI：
10.1164/rccm.201903-0615oc
发表时间：
2019-12-01
影响因子：
24.7
作者：
Ghosh, Arunava;Coakley, Raymond D.;Tarran, Robert
通讯作者：
Tarran, Robert
DOI：
10.1164/ajrccm.157.6.9707011
发表时间：
1998-06-01
影响因子：
24.7
作者：
Boers, JE;Ambergen, AW;Thunnissen, FBJM
通讯作者：
Thunnissen, FBJM
影响因子：
24.3
作者：
Amatngalim, Gimano D.;Schrumpf, Jasmijn A.;van der Does, Anne M.
通讯作者：
van der Does, Anne M.