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

Br J Pharmacol. 2006 Jan;147(2):225-34. doi: 10.1038/sj.bjp.0706467.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphibian Proteins / pharmacology*
  • Animals
  • Chemotaxis
  • Cytokines / metabolism*
  • Gastrointestinal Hormones / biosynthesis
  • In Vitro Techniques
  • Interleukin-12 / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neuropeptides / biosynthesis
  • Neuropeptides / pharmacology*
  • Receptors, G-Protein-Coupled / biosynthesis
  • Receptors, G-Protein-Coupled / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Amphibian Proteins
  • Bv8 protein, Bombina variegata
  • Cytokines
  • Gastrointestinal Hormones
  • Interleukin-1beta
  • Lipopolysaccharides
  • Neuropeptides
  • Prok2 protein, mouse
  • Receptors, G-Protein-Coupled
  • Tumor Necrosis Factor-alpha
  • Interleukin-12