PAR-2 regulates dental pulp inflammation associated with caries.
Protease-activated receptors (PARs) are G-protein-coupled receptors that are activated enzymatically by proteolysis of an N-terminal domain. The cleavage and activation of PARs by serine proteases represent a novel mechanism by which such enzymes could influence the host inflammatory response. The aim of this study was to determine whether PAR-2 expression and activation were increased in dental caries. Using immunohistochemistry, we showed PAR-2 to be localized to pulp cells subjacent to caries lesions, but minimally expressed by healthy pulp tissue. Trypsin and the PAR-2 agonist (PAR2-AP) activated PAR-2 in an in vitro functional assay. Endogenous molecules present in pulp cell lysates from carious teeth specifically activated PAR-2, but those from healthy teeth failed to do so. The activation of PAR-2 in vitro was shown to increase the expression of the pro-inflammatory mediator cyclo-oxygenase-2 (COX-2), providing a mechanism whereby PAR-2 could modulate pulpal inflammation.
Lundy
F T
FT
Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Whitla Medical Building, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom. f.lundy@qub.ac.uk
About
I
I
Curtis
T M
TM
McGahon
M K
MK
Linden
G J
GJ
Irwin
C R
CR
El Karim
I A
IA
D015153:Blotting, Western; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000032:analysis; D003731:Dental Caries / Q000378:metabolism* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D011671:Pulpitis / Q000378:metabolism* / Q000473:pathology; D044464:Receptor, PAR-2 / Q000819:agonists / Q000032:analysis*; D014357:Trypsin / Q000494:pharmacology
D018836:Inflammation Mediators; D044464:Receptor, PAR-2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D014357:Trypsin; D002118:Calcium