title: The role of migrating leukocytes in IL-1 beta-induced up-regulation of kinin B(1) receptors in rats.
abstract: 1. The present study examines the role of migrating leukocytes in the ability of IL-1 beta to induce the functional up-regulation of B(1) receptors, as assessed by kinin B(1) agonist-induced oedema in the rat paw. 2. Pre-treatment with the PAF receptor antagonist WEB 2086 inhibited des-Arg(9)-BK-induced oedema in IL-1 beta-treated paws, while the LTB(4) receptor antagonist CP105696 had no effect. Des-Arg(9)-BK-induced paw oedema was also inhibited by pre-treatment with the selectin blocker fucoidin or by an anti-CD-18 monoclonal antibody. 3. I.d. injection of IL-1 beta produced a 5 - 10-fold increase of myeloperoxidase (MPO) activity in the rat paw. The increase in MPO activity was significantly inhibited by WEB 2086 (46 +/- 9%), fucoidin (68 +/- 5%) or the CD-18 antibody (84 +/- 3%). In contrast, i.d. injection of TNF alpha a dose known to upregulate the B(1) receptor functionally did not induce any significant increase in MPO activity. 4. Des-Arg(9)-BK alone had no effect in MPO activity but enhanced (by about 40%) the response induced by IL-1 beta, an effect prevented by the B(1) receptor antagonist des-Arg(9)-[Leu(8)]-BK. 5. The concentration of TNF-alpha was increased in the paws after i.d. injection of IL-1 beta. Pre-treatment with fucoidin, WEB 2086, anti-CD-18 or CP 105695, significantly reversed the local increases in TNF-alpha concentrations (80 +/- 2; 75 +/- 4, 73 +/- 3 and 40 +/- 2%), respectively. 6. Finally, IL-1 beta induced an increase of B(1) receptor mRNA levels in the rat paw, an effect which was prevented by fucoidin treatment. 7. Taken together, these results indicate that up-regulation of B(1) receptors in the rat paw following IL-1 beta seems to involve the local recruitment of neutrophils and subsequent local TNF-alpha production. The cross-talk between kinins, cytokines and leukocytes implicate B(1) receptors in chronic inflammatory diseases.
authors.affiliation: Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88015-420 - Florianópolis, SC, Brazil.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.forename: Glória E P
authors.initials: GE
authors.lastname: de Souza
authors.forename: Natasha D
authors.initials: ND
authors.lastname: Ricci
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Pesquero
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D065168:Bradykinin Receptor Antagonists; D015815:Cell Adhesion Molecules; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D004487:Edema / Q000378:metabolism; D007271:Injections, Intradermal; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D065168:Bradykinin Receptor Antagonists; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; D009195:Peroxidase