Recombinant club cell protein 16 (CC16) ameliorates cigarette smoke‑induced lung inflammation in a murine disease model of COPD.
Recombinant club cell protein 16 (CC16) ameliorates cigarette smoke‑induced lung inflammation in a murine disease model of COPD.
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DOI：
10.3892/mmr.2018.9216
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发表时间：
2018-08
影响因子：
3.4
通讯作者：
Wang HL
中科院分区：
文献类型：
--
作者：
Pang M;Liu HY;Li T;Wang D;Hu XY;Zhang XR;Yu BF;Guo R;Wang HL
俱乐部细胞蛋白(Club cell Protein，CC16)主要由俱乐部细胞表达，具有抗炎功能，定位于细支气管上皮。以往的研究表明，CC16缺乏与慢性阻塞性肺疾病(COPD)的进展有关。本研究观察重组大鼠CC16蛋白对COPD小鼠的治疗作用，并探讨其作用机制。成年雄性C57/BL6小鼠30只，随机分为3组，每组10只。将20只小鼠暴露于香烟烟雾(CS)中24周，建立小鼠COPD模型。10只小鼠鼻腔注射rCC16(2.5微克/克体重)，对照组暴露于室内空气中。结果表明，rCC16治疗可减轻CS染毒所致小鼠肺组织的病理损伤，减少肺组织肿瘤坏死因子α、白介素6和白介素8的产生。给予rCC16后，COPD小鼠内源性CC16表达上调，体重增加，而CS染毒小鼠则相反。此外，rCC16可抑制肺组织中NF-κB/p65的DNA结合，减少肺泡灌洗液和肺上皮细胞中NF-κB/p65的核转位。此外，rCC16治疗导致包括巨噬细胞在内的BALF细胞总数减少，而COPD小鼠的BALF细胞总数升高。综上所述，本研究结果表明，rCC16通过下调促炎因子κB途径对慢性阻塞性肺疾病具有治疗作用。
Club cell protein (CC16) is expressed primarily by club cells possesses anti-inflammatory properties and is located in the bronchiolar epithelium. Previous studies have demonstrated that CC16 deficiency is associated with the progression of chronic obstructive pulmonary disease (COPD). In the present study, the therapeutic effects of recombinant rat CC16 protein in mice with COPD were examined and the underlying mechanisms investigated. A total of 30 adult male C57/BL6 mice were randomly divided into three groups (10 mice/group). A mouse COPD model was generated by exposing 20 mice to cigarette smoke (CS) for 24 weeks. A total of 10 mice were treated intranasally with rCC16 (2.5 µg/g body weight) and control mice were exposed to normal room air. Results indicated that rCC16 treatment ameliorated pathological damage in the lungs and reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8, which were induced by CS exposure. After rCC16 administration, endogenous CC16 was upregulated and the body weight of COPD mice was increased, whereas the opposite was observed in CS-exposed mice. Additionally, rCC16 treatment inhibited the DNA binding of NF-κB/p65 in lung tissues and reduced nuclear translocation of NF-κB/p65 in BALF and epithelial cells. Moreover, rCC16 treatment lead to a decrease in the total number of BALF cells, including macrophages, which was elevated in COPD mice. In conclusion, the present results demonstrate that rCC16 has therapeutic effects on COPD by downregulating pro-inflammatory factors via the NF-κB pathway.
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DOI：
10.2147/copd.s109243
发表时间：
2017
影响因子：
2.8
作者：
Ma R;Gong X;Jiang H;Lin C;Chen Y;Xu X;Zhang C;Wang J;Lu W;Zhong N
通讯作者：
Zhong N
影响因子：
13.5
作者：
Edwards MR;Bartlett NW;Clarke D;Birrell M;Belvisi M;Johnston SL
通讯作者：
Johnston SL
影响因子：
9.6
作者：
Gibson, PG;Simpson, JL;Saltos, N
通讯作者：
Saltos, N
影响因子：
14.2
作者：
Barnes, Peter J.
通讯作者：
Barnes, Peter J.
影响因子：
14.2
作者：
Barnes, Peter J.
通讯作者：
Barnes, Peter J.