Bv8, the amphibian homologue of the mammalian prokineticins, induces a proinflammatory phenotype of mouse macrophages

• Published in: British journal of pharmacology 2006-01, Vol.147 (2), p.225-234
• Main Authors: Martucci, Cataldo, Franchi, Silvia, Giannini, Elisa, Tian, Hui, Melchiorri, Pietro, Negri, Lucia, Sacerdote, Paola
• Format: Article
• Language: English
• Subjects: Amphibian Proteins - pharmacology; Animals; anti‐inflammatory cytokines; Biological and medical sciences; Bv8; Chemotaxis; Cytokines - metabolism; Gastrointestinal Hormones - biosynthesis; In Vitro Techniques; Interleukin-12 - metabolism; Interleukin-1beta - metabolism; Lipopolysaccharides - pharmacology; macrophages; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Knockout; Neuropeptides - biosynthesis; Neuropeptides - pharmacology; Pharmacology. Drug treatments; proinflammatory cytokines; prokineticins; Receptors, G-Protein-Coupled - biosynthesis; Receptors, G-Protein-Coupled - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0706467

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. 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. Bv8 induces potent chemotaxis of macrophages at concentrations as low as 10−12 M. 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. 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. Studies in PKR‐1 knockout mice indicate that all the activities exerted by Bv8 on macrophages are mediated by the PKR‐1 receptor. In conclusion, Bv8 appears to be able to induce the macrophage to migrate and to acquire a proinflammatory phenotype. British Journal of Pharmacology (2006) 147, 225–234. doi:10.1038/sj.bjp.0706467