title: Effect of acute and chronic inflammatory stimuli on expression of protease-activated receptors 1 and 2 in alveolar macrophages.
abstract: BACKGROUND
  Protease-activated receptors 1 and 2 (PAR-1 and PAR-2) are 7-transmembrane G protein-coupled receptors activated by serine proteases in many cell types, including monocytes-macrophages, leading to the production of pro-inflammatory mediators, cytokines, and growth factors.
  
  
  OBJECTIVE
  We determined the influence of chronic smoking and asthma on the expression of PAR-1 and PAR-2 receptors on alveolar macrophages (AMs).
  
  
  METHODS
  We used RT-PCR and immunocytochemistry with confocal microscopy to determine mRNA and protein expression of PAR-1 and PAR-2 in AMs obtained from healthy smokers, asthmatic patients, and healthy subjects. In addition, we examined the effect of IL-1beta and LPS.
  
  
  RESULTS
  PAR1 mRNA was decreased, whereas PAR2 mRNA was increased in 24-hour cultured AMs from smokers when compared with values in AMs from healthy subjects. Paradoxically, there was a higher degree of PAR-1 protein staining in AMs from smokers, whereas PAR-2 staining was similar in smokers and healthy subjects. PAR-1 and PAR-2 mRNA and protein expression were similar in asthmatic patients and control subjects. IL-1beta and LPS had no effect on PAR1 and PAR2 gene expression by AMs.
  
  
  CONCLUSIONS
  There is a dissociation between gene and protein expression of PAR-1 and PAR-2. PAR-1 protein overexpression in AMs from smokers might be important in the pathophysiology of chronic airways disease.
authors.affiliation: Department of Thoracic Medicine, Imperial College School of Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Roche
authors.forename: Robert G
authors.initials: RG
authors.lastname: Stirling
authors.forename: Sam
authors.initials: S
authors.lastname: Lim
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
authors.forename: Tim
authors.initials: T
authors.lastname: Oates
authors.forename: Elen
authors.initials: E
authors.lastname: Jazrawi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Caramori
authors.forename: K Fan
authors.initials: KF
authors.lastname: Chung
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000235:genetics / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin