Bv8, the amphibian homologue of the mammalian prokineticins, induces a pro-inflammatory 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-proteincoupled 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 Gq 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.