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Kocić, J; Santibañez, JF; Krstić, A; Mojsilović, S; Ilić, V; Bugarski, D.
Interleukin-17 modulates myoblast cell migration by inhibiting urokinase type plasminogen activator expression through p38 mitogen-activated protein kinase.
Int J Biochem Cell Biol. 2013; 45(2): 464-475. Doi: 10.1016/j.biocel.2012.11.010
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Krstic Jelena
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Abstract:
Interleukin-17 belongs to a family of pro-inflammatory cytokines with pleiotropic effects, which can be associated with several inflammatory diseases of the muscle tissue. Although elevated levels of interleukin-17 have been described in inflammatory myopathies, its role in muscle homeostasis remains to be elucidated. The requirement of the urokinase type plasminogen activator in skeletal myogenesis was recently demonstrated in vivo and in vitro, suggesting its involvement in the regulation of extracellular matrix remodeling, cell migration and myoblast fusion. Our previous results have demonstrated that interleukin-17 inhibits myogenic differentiation of C2C12 myoblasts in vitro concomitantly with the inhibition of cell migration. However, the involvement of urokinase type plasminogen activator in interleukin-17-inhibited myogenesis and migration remained to be analyzed. Therefore, the effect of interleukin-17 on the production of urokinase type plasminogen activator by C2C12 myoblasts was determined in the present study. Our results demonstrated that interleukin-17 strongly inhibits urokinase type plasminogen activator expression during myogenic differentiation. This reduction of urokinase type plasminogen activator production corresponded with the inhibition of cell migration by interleukin-17. Activation of p38 signaling pathway elicited by interleukin-17 mediated the inhibition of both urokinase type plasminogen activator expression and cell migration. Additionally, IL-17 inhibited C2C12 cells migration by causing the cells to reorganize their cytoskeleton and lose polarity. Therefore, our results suggest a novel mechanism by which interleukin-17 regulates myogenic differentiation through the inhibition of urokinase type plasminogen activator expression and cell migration. Accordingly, interleukin-17 may represent a potential clinical target worth investigating for the treatment of inflammatory muscle diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Actin Cytoskeleton - metabolism
Animals -
Cell Differentiation -
Cell Line -
Cell Movement -
Cell Proliferation -
Down-Regulation -
Enzyme Activation -
Extracellular Signal-Regulated MAP Kinases - metabolism
Imidazoles - pharmacology
Interleukin-17 - physiology
MAP Kinase Signaling System -
Mice -
Myoblasts - physiology
Pyridines - pharmacology
Transcriptional Activation -
Urokinase-Type Plasminogen Activator - genetics
Urokinase-Type Plasminogen Activator - metabolism
p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases - metabolism

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Myoblast
IL-17
p38
uPA
Migration
Differentiation
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