title: Cigarette smoke augments the expression and responses of toll-like receptor 3 in human macrophages.
abstract: OBJECTIVE
  Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD). Recently, toll-like receptor 3 (TLR3) was shown to recognize pathogen-associated molecular patterns, especially viral-derived double-stranded RNA, and to be involved in immune responses. However, the effects of cigarette smoke on TLR3 remain unclear. In this study, it was examined whether cigarette smoke affects the expression and responses of TLR3 in human macrophages.
  
  
  METHODS
  The expression of TLR3 in alveolar macrophages from human lung tissues was analysed by immunohistochemistry, and the correlation of TLR3 expression with smoking history and lung function was evaluated. In addition, the effect of cigarette smoke on the expression and responses of TLR3 in macrophage lineage cells was investigated.
  
  
  RESULTS
  TLR3-positive alveolar macrophage numbers were significantly increased in smokers and COPD patients compared with non-smoking control subjects, but there was no difference between smokers and COPD patients. TLR3-positive macrophage numbers were positively correlated with smoking history and inversely correlated with corrected carbon monoxide diffusing capacity, but were not correlated with % predicted forced expiratory volume in 1 s. Furthermore, cigarette smoke extract potentiated the expression of TLR3 in monocyte-derived macrophages and significantly augmented the release of interleukin-8, as well as total matrix metalloproteinase-9 activity, in cells treated with TLR3 ligand.
  
  
  CONCLUSIONS
  These data suggest that cigarette smoke augments the expression and responses of TLR3 in human macrophages, and this may contribute to neutrophilic airway inflammation and parenchymal destruction in the lungs of smokers and patients with COPD.
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. koarai@wakayama-med.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Koarai
authors.forename: Satoru
authors.initials: S
authors.lastname: Yanagisawa
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Sugiura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Akamatsu
authors.forename: Tsunahiko
authors.initials: T
authors.lastname: Hirano
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Kazuto
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Minakata
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D012129:Respiratory Function Tests; D012907:Smoking / Q000378:metabolism*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; C495344:TLR3 protein, human; D014028:Tobacco Smoke Pollution; D051196:Toll-Like Receptor 3; D020780:Matrix Metalloproteinase 9