Cigarette smoke-induced lung inflammation in COPD mediated via LTB4/BLT1/SOCS1 pathway.
Cigarette smoke-induced lung inflammation in COPD mediated via LTB4/BLT1/SOCS1 pathway.
复制标题
通过 LTB4/BLT1/SOCS1 通路介导香烟烟雾诱发 COPD 肺部炎症
DOI：
10.2147/copd.s96412
复制
发表时间：
2016
影响因子：
2.8
通讯作者：
He P
中科院分区：
文献类型：
--
作者：
Dong R;Xie L;Zhao K;Zhang Q;Zhou M;He P
研究背景有证据表明细胞因子信号转导抑制因子1（SOCS 1）在炎症的负性调节中起重要作用。我们在体外和临床样本中研究了吸烟、SOCS 1和白三烯B4（LTB 4）之间的关系，并检测了LTB 4受体1（BLT 1）拮抗剂对炎症的影响。方法采用免疫组化和实时荧光定量聚合酶链反应检测SOCS 1在支气管黏膜中的表达。采用真实的时间PCR法检测支气管肺泡灌洗液（BALF）中SOCS 1和BLT 1的表达，并采用酶联免疫吸附法检测BALF中细胞因子的水平。在体外实验中，采用实时荧光定量PCR和Western blot检测香烟烟雾提取物诱导的小鼠巨噬细胞系RAW 264. 7中SOCS 1的表达，并采用酶联免疫吸附法检测细胞培养上清中细胞因子的水平。然后，我们研究了BLT 1拮抗剂U-75302对这些细胞中SOCS 1表达的影响。结果COPD患者和非COPD对照组分别行支气管内活检（15例COPD患者和12例非COPD对照组）和支气管肺泡灌洗液（20例COPD患者和20例非COPD对照组）检查，结果显示COPD患者肺组织SOCS 1表达明显降低。COPD患者BALF中炎性细胞因子水平升高，且与SOCS 1水平呈负相关。此外，BLT 1拮抗剂恢复SOCS 1表达，进而抑制体外炎性细胞因子分泌。结论长期香烟烟雾暴露可导致SOCS 1降解和LTB 4蓄积，并与肺气肿和炎症相关。BLT 1拮抗剂可能是治疗COPD的潜在治疗候选物。
Background Evidence suggests that suppressor of cytokine signaling 1 (SOCS1) is crucial for the negative regulation of inflammation. We investigated the relationship between smoking, SOCS1, and leukotriene B4 (LTB4) in vitro and in clinical samples of COPD; besides which we detected the impact of LTB4 receptor 1 (BLT1) antagonist on inflammation. Methods SOCS1 expression in bronchial mucosa was determined by immunohistochemistry and real-time polymerase chain reaction. We also detect SOCS1 and BLT1 expression in alveolar macrophages from bronchoalveolar lavage fluid (BALF) by real time-PCR, in addition to measuring the level of cytokines in BALF using enzyme-linked immunosorbent assay. In vitro, we investigated the expression of SOCS1 in cigarette smoke extract-induced mouse macrophage cell line RAW264.7 by real-time polymerase chain reaction and Western blot, and detected the level of cytokines in the supernatant by enzyme-linked immunosorbent assay. Then, we investigated the effects of BLT1 antagonist U-75302 on SOCS1 expression in these cells. Results We obtained endobronchial biopsies (15 COPD patients and 12 non-COPD control subjects) and BALF (20 COPD patients and 20 non-COPD control subjects), and our results showed that SOCS1 expression significantly decreased in lung tissues from COPD patients. Inflammatory cytokines in BALF were higher in COPD and these inflammatory cytokines negatively correlate with SOCS1 levels. Further, the BLT1 antagonist restored SOCS1 expression and in turn inhibited inflammatory cytokine secretion in vitro. Conclusion Long-term cigarette smoke exposure induced SOCS1 degradation and LTB4 accumulation, which was associated with emphysema and inflammation. A BLT1 antagonist might be a potential therapeutic candidate for the treatment of COPD.