Bv8, the amphibian homologue of the mammalian prokineticins, induces a proinflammatory phenotype of mouse macrophages.
1.--The small protein Bv8, isolated from the amphibian skin, belongs to a novel family of secreted proteins linked to several biological effects. We describe the expression of Bv8/prokineticins and their receptors in mouse macrophages, and characterize their proinflammatory activities. 2.--The rodent analogue of Bv8, prokineticin-2, is expressed by macrophages, as well as its G-protein-coupled receptor prokineticin receptor (PKR-1 and PKR-2). PKR-1 is expressed more abundantly. 3.-- Bv8 induces potent chemotaxis of macrophages at concentrations as low as 10(-12) M. 4.-- It stimulates lipopolysaccharide-induced production of the proinflammatory cytokines IL-1 and IL-12, reducing that of the anti-inflammatory cytokine IL-10. The effects are observed starting at the very low concentration of 10(-11) M. 5.--Effects on chemotaxis and cytokine are not pertussis-toxin sensitive, but are completely prevented by addition of the phospholipase inhibitor U73122, suggesting a G(q) protein is involved in the Bv8-induced effects. 6.--Studies in PKR-1 knockout mice indicate that all the activities exerted by Bv8 on macrophages are mediated by the PKR-1 receptor. 7.--In conclusion, Bv8 appears to be able to induce the macrophage to migrate and to acquire a proinflammatory phenotype.
Martucci
Cataldo
C
Department of Pharmacology, University of Milan, via Vanvitelli 32, 20129 Milan, Italy.
Franchi
Silvia
S
Giannini
Elisa
E
Tian
Hui
H
Melchiorri
Pietro
P
Negri
Lucia
L
Sacerdote
Paola
P
D029845:Amphibian Proteins / Q000494:pharmacology*; D000818:Animals; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000096:biosynthesis; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009479:Neuropeptides / Q000096:biosynthesis / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D029845:Amphibian Proteins; C121344:Bv8 protein, Bombina variegata; D016207:Cytokines; D005768:Gastrointestinal Hormones; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009479:Neuropeptides; C486586:Prok2 protein, mouse; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12