Cigarette smoke-induced lung inflammation in COPD mediated via LTB4/BLT1/SOCS1 pathway

• Main Authors: Dong R, Xie L, Zhao K, Zhang Q, Zhou M, He P
• Format: Article
• Language: English
• Published: Dove Medical Press 2015-12-01
• Series: International Journal of COPD
• Subjects: chronic obstructive pulmonary disease; SOCS;LTB4; cigarette smoke; airway inflammation
• Online Access: https://www.dovepress.com/cigarette-smoke-induced-lung-inflammation-in-copd-mediated-via-ltb4blt-peer-reviewed-article-COPD

Ran Dong,1,* Liang Xie,1,* Kaishun Zhao,2,* Qiurui Zhang,1 Min Zhou,1 Ping He3 1Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 2Department of Respiratory Medicine, Jiading Central Hospital, 3Department of Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work 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. Keywords: treatment, LTB1 antagonist, endobronchial biopsies, BALF, inflammatory cytokines