Interleukin-17 modulates myoblast cell migration by inhibiting urokinase type plasminogen activator expression through p38 mitogen-activated protein kinase

2013 ◽  
Vol 45 (2) ◽  
pp. 464-475 ◽  
Author(s):  
Jelena Kocić ◽  
Juan F. Santibañez ◽  
Aleksandra Krstić ◽  
Slavko Mojsilović ◽  
Vesna Ilić ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Plasminogen Activator ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 17 ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Mitogen Activated Protein ◽  
Myoblast Cell

scholarly journals Role of Distinct Mitogen-Activated Protein Kinase Pathways and Cooperation between Ets-2, ATF-2, and Jun Family Members in Human Urokinase-Type Plasminogen Activator Gene Induction by Interleukin-1 and Tetradecanoyl Phorbol Acetate

1999 ◽  
Vol 19 (9) ◽  
pp. 6240-6252 ◽  
Author(s):  
Grazia Cirillo ◽  
Laura Casalino ◽  
Daniela Vallone ◽  
Anna Caracciolo ◽  
Dario De Cesare ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Plasminogen Activator ◽  
Mutational Analysis ◽  
Interleukin 1 ◽  
Mitogen Activated Protein Kinase ◽  
Transactivation Domain ◽  
Tetradecanoyl Phorbol Acetate ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Mitogen Activated Protein

ABSTRACT We have investigated the in vivo and in vitro regulation of the human urokinase-type plasminogen activator (uPA) gene by interleukin-1 (IL-1) and analyzed the transcription factors and signalling pathways involved in the response of the −2.0-kb uPA enhancer to IL-1 induction and to tetradecanoyl phorbol acetate (TPA) induction. Mutational analysis showed the cooperative activity of the Ets-binding site (EBS) and the two AP-1 elements of the enhancer. The results reveal that the EBS is required for the response to both inducers mediated by Ets-2, which is regulated at a level subsequent to DNA binding, by an IL-1- and phorbol ester-inducible transactivation domain. Both the IL-1 and the TPA-mediated induction result in a drastic increase of AP-1 binding to the downstream site of the enhancer (uPA 3′ TPA-responsive element), while a mostly qualitative change, resulting from the interplay between ATF-2 homodimers and c-Jun–ATF-2 heterodimers, takes place at the upstream AP-1 element. The analysis of two distinct mitogen-activated protein kinase pathways shows that stress-activated protein kinase–Jun N-terminal kinase activation, resulting in the phosphorylation of ATF-2, c-Jun, and JunD, is required not only for the IL-1- but also for the TPA-dependent induction, while the extracellular signal-related kinase 1 (ERK-1) and ERK-2 activation is involved in the TPA- but not in the IL-1-dependent stimulation of the uPA enhancer.

scholarly journals Specific Activation of Mitogen-activated Protein Kinase by Transforming Growth Factor-β Receptors in Lipid Rafts Is Required for Epithelial Cell Plasticity

2009 ◽  
Vol 20 (3) ◽  
pp. 1020-1029 ◽  
Author(s):  
Wei Zuo ◽  
Ye-Guang Chen
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Protein Kinase ◽  
Lipid Rafts ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Coated Pits ◽  
Mapk Activation ◽  
Mitogen Activated Protein

Transforming growth factor (TGF)-β regulates a spectrum of cellular events, including cell proliferation, differentiation, and migration. In addition to the canonical Smad pathway, TGF-β can also activate mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and small GTPases in a cell-specific manner. Here, we report that cholesterol depletion interfered with TGF-β–induced epithelial-mesenchymal transition (EMT) and cell migration. This interference is due to impaired activation of MAPK mediated by cholesterol-rich lipid rafts. Cholesterol-depleting agents specifically inhibited TGF-β–induced activation of extracellular signal-regulated kinase (ERK) and p38, but not Smad2/3 or Akt. Activation of ERK or p38 is required for both TGF-β–induced EMT and cell migration, whereas PI3K/Akt is necessary only for TGF-β–promoted cell migration but not for EMT. Although receptor heterocomplexes could be formed in both lipid raft and nonraft membrane compartments in response to TGF-β, receptor localization in lipid rafts, but not in clathrin-coated pits, is important for TGF-β–induced MAPK activation. Requirement of lipid rafts for MAPK activation was further confirmed by specific targeting of the intracellular domain of TGF-β type I receptor to different membrane locations. Together, our findings establish a novel link between cholesterol and EMT and cell migration, that is, cholesterol-rich lipid rafts are required for TGF-β–mediated MAPK activation, an event necessary for TGF-β–directed epithelial plasticity.

scholarly journals Estramustine Phosphate Inhibits TGF-β-Induced Mouse Macrophage Migration and Urokinase-Type Plasminogen Activator Production

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Sonja S. Mojsilovic ◽  
Slavko Mojsilovic ◽  
Suncica Bjelica ◽  
Juan F. Santibanez
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Plasminogen Activator ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Raw 264.7 ◽  
Estramustine Phosphate ◽  
Macrophage Cell ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Transforming growth factor-beta (TGF-β) has been demonstrated as a key regulator of immune responses including monocyte/macrophage functions. TGF-β regulates macrophage cell migration and polarization, as well as it is shown to modulate macrophage urokinase-type plasminogen activator (uPA) production, which also contributes to macrophage chemotaxis and migration toward damaged or inflamed tissues. Microtubule (MT) cytoskeleton dynamic plays a key role during the cell motility, and any interference on the MT network profoundly affects cell migration. In this study, by using estramustine phosphate (EP), which modifies MT stability, we analysed whether tubulin cytoskeleton contributes to TGF-β-induced macrophage cell migration and uPA expression. We found out that, in the murine macrophage cell line RAW 264.7, EP at noncytotoxic concentrations inhibited cell migration and uPA expression induced by TGF-β. Moreover, EP greatly reduced the capacity of TGF-β to trigger the phosphorylation and activation of its downstream Smad3 effector. Furthermore, Smad3 activation seems to be critical for the increased cell motility. Thus, our data suggest that EP, by interfering with MT dynamics, inhibits TGF-β-induced RAW 264.7 cell migration paralleled with reduction of uPA induction, in part by disabling Smad3 activation by TGF-β.

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