title: Cigarette smoke-induced lung inflammation in COPD mediated via LTB4/BLT1/SOCS1 pathway.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Dong
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, Jiading Central Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Qiurui
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D000368:Aged; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D005233:Fatty Alcohols / Q000494:pharmacology*; D005260:Female; D006018:Glycols / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D011656:Pulmonary Emphysema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
chemical_list: D005233:Fatty Alcohols; D006018:Glycols; C513240:LTB4R protein, human; D018102:Receptors, Leukotriene B4; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C062137:U 75302; D007975:Leukotriene B4
keywords: BALF; LTB1 antagonist; endobronchial biopsies; inflammatory cytokines; treatment