Role of chemokine C-C motif ligand-1 in acute and chronic pulmonary inflammations.
Role of chemokine C-C motif ligand-1 in acute and chronic pulmonary inflammations.
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DOI：
10.1186/s40064-016-2904-z
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Kubota I
中科院分区：
文献类型：
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作者：
Kishi H;Sato M;Shibata Y;Sato K;Inoue S;Abe S;Kimura T;Nishiwaki M;Yamauchi K;Nemoto T;Igarashi A;Tokairin Y;Nakajima O;Kubota I
趋化因子C-C基序配体1（CCL 1）将C-C基序趋化因子受体8阳性白细胞聚集到炎症部位。趋化因子CCL1基因单核苷酸多态性与慢性阻塞性肺疾病加重相关但CCL1在肺部炎症过程中是否具有免疫调节功能尚不清楚。本研究旨在使用新产生的在肺中表达CCL1的转基因小鼠（SPC-CCL1小鼠）来阐明这一问题。为了评价这些小鼠的表型，进行肺切片和支气管肺泡灌洗液（BAL）分析。我们分别用脂多糖（LPS）或牛分枝杆菌作为急性或慢性肺部炎症模型。在静息条件下和LPS给药后，在来自SPC-CCL1 Tg和野生型小鼠的肺组织之间未观察到组织学差异。在静息状态下，SPC-CCL1 Tg小鼠的总BAL细胞浓度低于野生型小鼠（P = 0.0097）。流式细胞术分析显示，SPC-CCL1 Tg小鼠的F4/80阳性细胞比野生型小鼠少（P = 0.0278）。经气管内注射LPS后，CCL1过表达既不改变BAL细胞的总数，也不改变BAL细胞的群体。分枝杆菌给药后，肺肉芽肿形成明显增强。与野生型小鼠相比，在用分枝杆菌处理的SPC-CCL 1小鼠的肉芽肿区域中，内质网至核信号传导1（与肉芽肿形成和内质网应激相关的分子）的免疫染色程度显著增强。CCL1在肺中的过表达并没有改变LPS诱导的急性炎症反应，但在分枝杆菌治疗后增强了肉芽肿形成，这可能是通过增强内质网应激。
Chemokine C-C motif ligand 1 (CCL1) accumulates C-C motif chemokine receptor 8 positive leukocytes to the inflammatory sites. Single-nucleotide polymorphisms in the chemokine CCL1 gene are associated with exacerbation of chronic obstructive lung disease. However, it is unclear whether CCL1 has immunomodulatory functions during pulmonary inflammation. This study aimed to elucidate this issue using newly generated transgenic mice that express CCL1 in the lungs (SPC-CCL1 mice). To evaluate the phenotypes of these mice, lung section and bronchoalveolar lavage (BAL) fluid analyses were performed. We intratracheally administered lipopolysaccharide (LPS) or Mycobacterium bovis as a model of acute or chronic lung inflammation, respectively. No histological differences were observed between lung tissue from SPC-CCL1 Tg and wild-type mice in the resting condition and after LPS administration. In the resting condition, the total BAL cell concentration was lower in SPC-CCL1 Tg mice than in wild-type mice (P = 0.0097). Flow cytometric analyses showed that SPC-CCL1 Tg mice had fewer F4/80-positive cells than wild-type mice (P = 0.0278). After intratracheal LPS administration, CCL1 overexpression changed neither the total numbers nor population of BAL cells. After mycobacterial administration, pulmonary granuloma formation was significantly enhanced. The degree of Immunostaining for endoplasmic reticulum to nucleus signaling 1, a molecule associated with granuloma formation and endoplasmic reticulum stress, was significantly enhanced in the granuloma regions of SPC-CCL1 mice treated with Mycobacterium, compared to those of wild-type mice. CCL1 overexpression in the lungs did not change the acute inflammatory response induced by LPS, but enhanced granuloma formation after mycobacterial treatment, possibly through enhancing endoplasmic reticulum stress.