Enhancement of macrophage inflammatory responses by CCL2 is correlated with increased miR-9 expression and downregulation of the ERK1/2 phosphatase Dusp6
| Autor: | Steven L. Kunkel, Katherine A. Gallagher, Sarah E. Salter-Green, William F. Carson, Amrita Joshi, Melissa Scola |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Regulation of gene expression Chemokine Immunology Macrophage polarization DUSP6 Biology Article Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Downregulation and upregulation 030220 oncology & carcinogenesis biology.protein Macrophage Signal transduction Macrophage inflammatory protein |
| Popis: | Macrophage polarization plays a central role in both protective immunity and immunopathology. While the role of cytokines in driving macrophage polarization is well characterized, less is understood about the role of chemokines. The purpose of this study was to determine if C-C chemokine 2 (CCL2/MCP1) could influence macrophage polarization in response to subsequent activation with cytokin es and microbial products. Treatment of bone marrow-derived macrophages with CCL2 alone did not result in increased expression of either classical or alternatively-activated macrophage genes as compared to standard skewing cytokines or Tolllike receptor agonists. However, subsequent stimulation of CCL2 pre-treated macrophages with classical activation stimuli resulted in enhanced expression of genes associated with classical activation. This enhancement correlated with increased phosphorylation of ERK1/2 kinases, a decrease in expression of the ERK phosphatase Dusp6 and enhanced expression of miR-9. These results indicate that CCL2 supports the classical activation of macrophages, with miR-9 mediated down-regulation of Dusp6 and enhanced ERK-mediated signal transduction possibly mediating this enhanced pro-inflammatory gene expression. |
| Databáze: | OpenAIRE |
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