title: Urokinase type plasminogen activator mediates Interleukin-17-induced peripheral blood mesenchymal stem cell motility and transendothelial migration.
abstract: Mesenchymal stem cells (MSCs) have the potential to migrate toward damaged tissues increasing tissue regeneration. Interleukin-17 (IL-17) is a proinflammatory cytokine with pleiotropic effects associated with many inflammatory diseases. Although IL-17 can modulate MSC functions, its capacity to regulate MSC migration is not well elucidated so far. Here, we studied the role of IL-17 on peripheral blood (PB) derived MSC migration and transmigration across endothelial cells. IL-17 increased PB-MSC migration in a wound healing assay as well as cell mobilization from collagen gel. Concomitantly IL-17 induced the expression of urokinase type plasminogen activator (uPA) without affecting matrix metalloproteinase expression. The incremented uPA expression mediated the capacity of IL-17 to enhance PB-MSC migration in a ERK1,2 MAPK dependent way. Also, IL-17 induced PB-MSC migration alongside with changes in cell polarization and uPA localization in cell protrusions. Moreover, IL-17 increased PB-MSC adhesion to endothelial cells and transendothelial migration, as well as increased the capacity of PB-MSC adhesion to fibronectin, in an uPA-dependent fashion. Therefore, our data suggested that IL-17 may act as chemotropic factor for PB-MSCs by incrementing cell motility and uPA expression during inflammation development.
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Krstić
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Hristina
authors.initials: H
authors.lastname: Obradović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jauković
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Okić-Đorđević
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Drenka
authors.initials: D
authors.lastname: Trivanović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Kukolj
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Slavko
authors.initials: S
authors.lastname: Mojsilović
authors.affiliation: Laboratory for Immunology, Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilić
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia. Electronic address: jfsantibanez@imi.bg.ac.rs.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Santibañez
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells Institute for Medical Research, University of Belgrade, Dr Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Diana
authors.initials: D
authors.lastname: Bugarski
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D016764:Cell Polarity / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases
keywords: Interleukin-17; Migration; Peripheral blood mesenchymal stem cells; Transendothelial migration; Urokinase type plasminogen activator