scholarly journals Lipopolysaccharide-Induced Matrix Metalloproteinase-9 Expression Associated with Cell Migration in Rat Brain Astrocytes

2019 ◽  
Vol 21 (1) ◽  
pp. 259 ◽  
Author(s):  
Chien-Chung Yang ◽  
Chih-Chung Lin ◽  
Li-Der Hsiao ◽  
Jing-Ming Kuo ◽  
Hui-Ching Tseng ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Matrix Metalloproteinase ◽  
Rat Brain ◽  
P38 Map Kinase ◽  
Tanshinone Iia ◽  
Mitogen Activated Protein Kinase ◽  
Brain Diseases ◽  
Amino Terminal ◽  
Tyrosine Kinase 2

Neuroinflammation is a landmark of neuroinflammatory and neurodegenerative diseases. Matrix metalloproteinase (MMP)-9, one member of MMPs, has been shown to contribute to the pathology of these brain diseases. Several experimental models have demonstrated that lipopolysaccharide (LPS) exerts a pathological role through Toll-like receptors (TLRs) in neuroinflammation and neurodegeneration. However, the mechanisms underlying LPS-induced MMP-9 expression in rat brain astrocytes (RBA-1) are not completely understood. Here, we applied pharmacological inhibitors and siRNA transfection to assess the levels of MMP-9 protein, mRNA, and promoter activity, as well as protein kinase phosphorylation in RBA-1 cells triggered by LPS. We found that LPS-induced expression of pro-form MMP-9 and cell migration were mediated through TLR4, proto-oncogene tyrosine-protein kinase (c-Src), proline-rich tyrosine kinase 2 (Pyk2), platelet-derived growth factor receptor (PDGFR), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), p38 mitogen-activated protein kinase (MAPK), and Jun amino-terminal kinase (JNK)1/2 signaling molecules in RBA-1 cells. In addition, LPS-stimulated binding of c-Jun to the MMP-9 promoter was confirmed by chromatin immunoprecipitation (ChIP) assay, which was blocked by pretreatment with c-Src inhibitor II, PF431396, AG1296, LY294002, Akt inhibitor VIII, p38 MAP kinase inhibitor VIII, SP600125, and tanshinone IIA. These results suggest that in RBA-1 cells, LPS activates a TLR4/c-Src/Pyk2/PDGFR/PI3K/Akt/p38 MAPK and JNK1/2 pathway, which in turn triggers activator protein 1 (AP-1) activation and ultimately induces MMP-9 expression and cell migration.

HIV-1 gp120 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent, pertussis toxin–insensitive chemokine receptor signaling

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 2909-2916 ◽  
Author(s):  
Manuela Del Corno ◽  
Qing-Hua Liu ◽  
Dominique Schols ◽  
Erik de Clercq ◽  
Sandra Gessani ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Pertussis Toxin ◽  
Chemokine Receptor ◽  
Calcium Release ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Infection ◽  
Amino Terminal ◽  
Crac Channels ◽  
Mitogen Activated Protein ◽  
Hiv 1

Abstract Human immunodeficiency virus type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry. It was recently demonstrated that HIV-1 glycoprotein 120 (gp120) elevated calcium and activated several ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. This study shows that chemokine receptor engagement by both CCR5-dependent (R5) and CXCR4-dependent (X4) gp120 led to rapid phosphorylation of the focal adhesion-related tyrosine kinase Pyk2 in macrophages. Pyk2 phosphorylation was also induced by macrophage inflammatory protein-1β (MIP-1β) and stromal cell–derived factor-1α, chemokine ligands for CCR5 and CXCR4. Activation was blocked by EGTA and by a potent blocker of calcium release–activated Ca++(CRAC) channels, but was insensitive to pertussis toxin (PTX), implicating CRAC-mediated extracellular Ca++ influx but not Gαi protein-dependent mechanisms. Coreceptor engagement by gp120 and chemokines also activated 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase/stress-activated protein kinase and p38 MAPK. Furthermore, gp120-stimulated macrophages secreted the chemokines monocyte chemotactic protein-1 and MIP-1β in a manner that was dependent on MAPK activation. Thus, the gp120 signaling cascade in macrophages includes coreceptor binding, PTX-insensitive signal transduction, ionic signaling including Ca++ influx, and activation of Pyk2 and MAPK pathways, and leads to secretion of inflammatory mediators. HIV-1 Env signaling through these pathways may contribute to dysregulation of uninfected macrophage functions, new target cell recruitment, or modulation of macrophage infection.

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.

Role of Adenosine Monophosphate-Activated Protein Kinase on Cell Migration, Matrix Contraction, and Matrix Metalloproteinase-1 and Matrix Metalloproteinase-2 Production in Nasal Polyp–Derived Fibroblasts

2017 ◽  
Vol 31 (6) ◽  
pp. 357-363 ◽  
Author(s):  
Ti-Young Um ◽  
Seoung-Ae Lee ◽  
Joo-Hoo Park ◽  
Jae-Min Shin ◽  
Il-Ho Park ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Matrix Metalloproteinase ◽  
Nasal Polyp ◽  
Nasal Polyps ◽  
Tissue Remodeling ◽  
Adenosine Monophosphate ◽  
Compound C ◽  
Matrix Contraction

Purpose Activation of adenosine monophosphate-activated protein kinase (AMPK) by metformin, as a master regulator of metabolism, is involved in airway tissue remodeling. Here, we investigated the physical role of AMPK on cell migration, matrix contraction, and the production of matrix metalloproteinases (MMP) in nasal polyp–derived fibroblasts (NPDF). Methods Primary NPDFs from six patients with chronic rhinosinusitis and nasal polyps were isolated and cultured. To assess the effect of AMPK on fibroblast migration, we conducted scratch and migration assays in NPDF treated with metformin and/or compound C. A collagen gel contraction assay measured activity of contractile. MMP expression was measured with reverse transcription-polymerase chain reaction, Western blot, and zymography. To evaluate for specific AMPK action, we examined by AMPK small interfering RNA. Results Metformin, an activator of AMPK, significantly inhibited cell migration in NPDFs in a dose-dependent manner. Compound C, an inhibitor of AMPK, partially reversed the inhibitory effect of metformin. Metformin also significantly decreased contractile activity, with a concomitant reduction in the production of MMP-1 and MMP-2 but not of MMP-9. Specific silencing that targeted AMPK resulted in the enhancement of mobility and contractility and in the production of MMP-1 and MMP-2. Conclusion AMPK played an important role in regulating cell migration, matrix contraction, and MMP production in NPDFs, which provided data that AMPK activator might be a therapeutic target for the prevention of tissue remodeling in nasal polyps.

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