title: Soluble fractalkine prevents monocyte chemoattractant protein-1-induced monocyte migration via inhibition of stress-activated protein kinase 2/p38 and matrix metalloproteinase activities.
abstract: In this study, we address the question of the cross-talk between two chemokines that are cosecreted during inflammation, namely monocyte chemoattractant protein-1 (MCP-1) and soluble fractalkine (s-FKN), toward monocyte migration. We found that s-FKN fails to induce MonoMac6 cell migration per se. Interestingly, this chemokine antagonizes transendothelial migration and chemotaxis of MonoMac6 cells and freshly isolated human monocytes induced by MCP-1, indicating a direct effect of s-FKN on monocytic cells. In this study, we found that stress-activated protein kinase (SAPK)1/c-Jun N-terminal kinase 1 and SAPK2/p38 are involved in the control of MCP-1-induced MonoMac6 cell migration. We demonstrated that s-FKN abrogates the MCP-1-induced SAPK2/p38 activation as well as the upstream Pyk2 activity. Furthermore, we observed that s-FKN also inhibits the activity of a major matrix metalloproteinase (MMP), namely MMP-2. Taken collectively, our results indicate that the s-FKN antagonizes the chemoattractant effect of MCP-1 on monocytes, likely by inhibiting crucial signaling pathways, like SAPK2/p38 and MMP-2 activities.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 364, Institut Féderatif de Recherche 50, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 02, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vitale
authors.forename: Annie
authors.initials: A
authors.lastname: Schmid-Alliana
authors.forename: Véronique
authors.initials: V
authors.lastname: Breuil
authors.forename: Manuel
authors.initials: M
authors.lastname: Pomeranz
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Millet
authors.forename: Bernard
authors.initials: B
authors.lastname: Rossi
authors.forename: Heidy
authors.initials: H
authors.lastname: Schmid-Antomarchi
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition; D002469:Cell Separation; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D004790:Enzyme Induction / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051418:Focal Adhesion Kinase 2; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D012995:Solubility; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2