title: Prokineticin 1 induces CCL4, CXCL1 and CXCL8 in human monocytes but not in macrophages and dendritic cells.
abstract: Prokineticin 1 and 2 (PROK1 and PROK2) are two small proteins largely expressed in inflammatory tissues and involved in monocyte activation and differentiation. The focus of this study was to evaluate whether PROK1 was able to induce chemokine secretion in human monocytes, in monocyte-derived macrophages and in monocyte-derived dendritic cells, an aspect not addressed thus far. Here, we show for the first time, using flow cytometry, that PROK receptors 1 and 2 are present on the surface of human monocytes. Subsequently, monocytes were selected to investigate the chemokine response after stimulation by PROK1. Our results show that only three chemokines (CCL4, CXCL1 and CXCL8) were significantly induced at both the transcript and protein level, and that PROK1 induces most potently CXCL8, in a dose-dependent manner. From a mechanistic point of view, by blocking independently Galphai protein or intracellular calcium, monocytes lose the ability to secrete CXCL8 in response to PROK1. Finally, we observed that CCL4, CXCL1 and CXCL8 secretion, following PROK1 induction, is only observed in monocytes and not in monocyte-derived macrophages and dendritic cells. Our results demonstrate that, in vitro, the differentiation status of monocytes influences chemokine production after stimulation by PROK1, and that this chemokine production is geared toward a pro-inflammatory response. This could represent a novel amplification loop of leukocyte recruitment, extravasation and tissue invasion.
authors.affiliation: INSERM U620; Université de Rennes 1, IFR140, Rennes, France.
authors.forename: Justin
authors.initials: J
authors.lastname: Monnier
authors.forename: Véronique
authors.initials: V
authors.lastname: Quillien
authors.forename: Claire
authors.initials: C
authors.lastname: Piquet-Pellorce
authors.forename: Claudine
authors.initials: C
authors.lastname: Leberre
authors.forename: Laurence
authors.initials: L
authors.lastname: Preisser
authors.forename: Hugues
authors.initials: H
authors.lastname: Gascan
authors.forename: Michel
authors.initials: M
authors.lastname: Samson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054407:Chemokine CCL4 / Q000235:genetics / Q000378:metabolism*; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000494:pharmacology*
chemical_list: C066507:CCL4 protein, human; C475829:CXCL1 protein, human; C508606:CXCL8 protein, human; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D016209:Interleukin-8; D008070:Lipopolysaccharides; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived