Protease-activated receptor-2 activating peptide SLIGRL inhibits bacterial lipopolysaccharide-induced recruitment of polymorphonuclear leukocytes into the airways of mice.
Protease-activated receptor-2 (PAR2) acts as a receptor for trypsin and trypsin-like enzymes. The role of this receptor in airway inflammation is uncertain. In this study we assessed the effect of activation of PAR2 following intranasal administration of the peptide activator of PAR2, SLIGRL, over 72 h in mice. The extent of immune cell infiltration into the airways and activities of matrix metalloprotease-2 (MMP-2) and MMP-9 were assessed in bronchoalveolar lavage (BAL) by differential cell counts and gelatin zymography, respectively. SLIGRL did not cause a change in the number or types of cells retrieved in BAL at any time point and did not alter the levels of MMP-2 and MMP-9 present in BAL. In contrast, similar intranasal administration of bacterial lipopolysaccharide (LPS) caused a large influx of neutrophilic polymorphonuclear leukocytes, which was associated with increased MMP-2 at 3 h only and MMP-9 activity from 3-72 h. Simultaneous administration of SLIGRL and LPS transiently potentiated increased MMP-9 activity at 3 h but markedly inhibited neutrophil influx and elevated MMP-2 activity at 3 h. These findings suggest that PAR2 agonists may be useful therapeutic molecules in pulmonary inflammatory diseases.
Moffatt
James D
JD
Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia. jdm@unimelb.edu.au
Jeffrey
Kate L
KL
Cocks
Thomas M
TM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000819:agonists*; D014357:Trypsin / Q000378:metabolism
D008070:Lipopolysaccharides; D009842:Oligopeptides; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C099570:seryl-leucyl-isoleucyl-glycyl-arginyl-leucine; D014357:Trypsin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9