TY - JOUR
T1 - Effect of acute and chronic inflammatory stimuli on expression of protease-activated receptors 1 and 2 in alveolar macrophages
AU - Roche, Nicolas
AU - Stirling, Robert G.
AU - Lim, Sam
AU - Oliver, Brian G.
AU - Oates, Tim
AU - Jazrawi, Elen
AU - Caramori, Gaetano
AU - Chung, K. Fan
PY - 2003/2/1
Y1 - 2003/2/1
N2 - 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 proinflammatory 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-1β 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-1β 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.
AB - 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 proinflammatory 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-1β 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-1β 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.
KW - Alveolar macrophages
KW - Asthma
KW - Chronic airways disease
KW - Protease-activated receptors
UR - http://www.scopus.com/inward/record.url?scp=0037327047&partnerID=8YFLogxK
U2 - 10.1067/mai.2003.6
DO - 10.1067/mai.2003.6
M3 - Article
C2 - 12589358
AN - SCOPUS:0037327047
SN - 0091-6749
VL - 111
SP - 367
EP - 373
JO - The Journal of Allergy and Clinical Immunology
JF - The Journal of Allergy and Clinical Immunology
IS - 2
ER -