In vivo up-regulation of kinin B1 receptors after treatment with Porphyromonas gingivalis lipopolysaccharide in rat paw.
It has been demonstrated that kinin B(1) receptors are highly up-regulated under several stressful stimuli, such as infection. However, there is no evidence indicating whether Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) might lead to B(1) receptor up-regulation. In this study, we demonstrate that Pg-LPS injection into the rat paw resulted in a marked functional up-regulation of B(1) receptors (as measured by an increase of B(1) receptor-induced edema), which was preceded by a rapid rise in B(1) receptor mRNA expression. The local administration of Pg-LPS also resulted in a prominent production of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha), followed by an increase of neutrophil influx; both events were observed at periods before B(1) receptor induction. The functional and molecular Pg-LPS-elicited B(1) receptor up-regulation was significantly reduced by the glucocorticoid dexamethasone (0.5 mg/kg s.c.), and to a lesser extent by the chimeric anti-TNF-alpha antibody infliximab (1 mg/kg s.c.). Of high relevance, we show for the first time that a single administration of the proresolution lipid mediator (5S,12R,18R)-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid (resolvin E1; 300 ng/rat i.p.) was able to markedly down-regulate Pg-LPS-driven B(1) receptor expression, probably by inhibiting TNF-alpha production and neutrophil migration. Collectively, the present findings clearly suggest that Pg-LPS is able to induce the up-regulation of B(1) receptors through mechanisms involving TNF-alpha release and neutrophil influx, which are largely sensitive to resolvin E1. It is tempting to suggest that kinin B(1) receptors might well represent a pivotal pathway for the inflammatory responses evoked by P. gingivalis and its virulence factors.
Dornelles
Fabiana N
FN
Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Partenon, 90619-900, Porto Alegre, Brazil.
Santos
Diógenes S
DS
Van Dyke
Thomas E
TE
Calixto
João B
JB
Batista
Eraldo L
EL
Campos
Maria M
MM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005528:Foot / Q000473:pathology; D000069285:Infliximab; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000737:chemistry*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000096:biosynthesis* / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; C024626:bradykinin, des-Arg(9)-; D003907:Dexamethasone; D015118:Eicosapentaenoic Acid; D000069285:Infliximab; D009195:Peroxidase; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid; D001920:Bradykinin