Cytokine properties of prokineticins

Abstract

Prokineticins are a novel family of secreted peptides with diverse regulatory roles, one of which is their capacity to modulate immunity in humans and in other species. Prokineticins are small peptides of 8 kDa that mediate their biological activities by signaling through two homologous G‐protein‐coupled receptors (prokineticin receptor 1 and prokineticin receptor 2). This family of peptides is characterized by a completely conserved N‐terminal hexapeptide crucial for their bioactivities and a unique structural motif comprising five disulfide bonds. Prokineticins and their receptors are highly expressed in bone marrow, in peripheral circulating leukocytes, in inflamed tissues and in resident organ immune cells. Their structure, size, signaling and biological activities are reminiscent of the chemokine superfamily. In this review, emphasis is placed on the properties of prokineticins as cytokines and their role in the immune system.

The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain

“…Because prokineticins are potent chemoattractans for monocytes and macrophages both in vitro and in vivo and are able to stimulate the release of proinflammatory and proalgesic cytokines from macrophages (17)(18)(19)(20) and monocytes (28) we can further hypothesize that PK2, released at the site of inflammation, represents a component of the cytokine-chemokine loop in inflammatory pain, which is initiated by the arrival of granulocyte and maintained by the subsequent recruitment of monocytes and macrophages. Inflammatory stimuli activate the release of the cytokine G-CSF that stimulates the synthesis and release of the chemokine PK2 by neutrophils, and this chemokine, in turn, stimulates macrophage chemotaxis and cytokine release by recruited macrophages.…”

Crustacean hematopoiesis and the astakine cytokines

“…51 These different biologic roles of vertebrate PROKs have been extensively reviewed. [52][53][54] More interestingly, from an immunologic point of view, PROKs are differentially expressed within immune cells and play roles in vertebrate hematopoiesis in addition to acting as potent agents to induce angiogenesis and proinflammatory immune responses. [55][56][57] PROK1 induces differentiation of murine and human BM cells into the monocyte/macrophage lineage, 51,58 whereas PROK2 has similar effects on monocyte lineage.…”

An ancient cytokine, astakine, mediates circadian regulation of invertebrate hematopoiesis

“…Prokineticins (PROKs) belong to a family of small secreted proteins of about 80 amino acids originally isolated from the venom of the black mamba, Dendroaspis polylepis in 1980 as the nontoxic MIT1 peptide [11], and later the Bv8 peptide from skin secretions of the frog Bombina variegata [12]. During recent years several different biological activities associated with vertebrate PROKs have been discovered and they influence processes related to development of the nervous system as well as to immunity [13][14][15][16][17]. Vertebrate PROKs are usually highly expressed in inflammatory tissues and have numerous characters in common with cytokines [14], and for example the rodent PROK, Bv8 induce migration of macrophages [17].…”