Lipoteichoic acid from Staphylococcus aureus increases matrix metalloproteinase 9 expression in RAW 264.7 macrophages: Modulation by A2A and A2B adenosine receptors
| Autor: | Ismael Pretto Sauter, Marcela Moreira de Souza, Luiz Fernando de Souza, Fabiano Barreto, Rogério Margis, Elena Aida Bernard, Fernanda Rafaela Jardim |
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| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
MAPK/ERK pathway Staphylococcus aureus medicine.medical_specialty Time Factors Receptor Adenosine A2A MAP Kinase Kinase 4 MAP Kinase Signaling System Immunology Biology Matrix metalloproteinase Receptor Adenosine A2B p38 Mitogen-Activated Protein Kinases Gene Expression Regulation Enzymologic Cell Line Mice Internal medicine medicine Animals Humans Secretion Enzyme Inhibitors Protein kinase A Receptor Molecular Biology Kinase Macrophages Staphylococcal Infections Molecular biology Adenosine receptor Rats Teichoic Acids Endocrinology Matrix Metalloproteinase 9 Gene Knockdown Techniques lipids (amino acids peptides and proteins) Lipoteichoic acid |
| Zdroj: | Molecular Immunology. 46:937-942 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/j.molimm.2008.09.012 |
| Popis: | Peptidoglycan (PEG) and lipoteichoic acid (LTA) are the main constituents of Gram-positive bacteria cell wall and are described to modulate immune functions. Increased levels of matrix metalloproteinases (MMPs) were described in endotoxemia, suggesting that they participate to tecidual damage, multiple organs failure and vascular disfunction. Staphylococcus aureus PEG is described to increase MMPs 2 and 9 levels in plasma from rat and MMP 9 secretion by human neutrophils, however, the effect of LTA on MMPs is unknown. In this work, was evaluated the modulation of MMPs 2 and 9 expression and secretion in RAW 264.7 macrophages by LTA from S. aureus. The role of A2A and A2B adenosine receptors was also investigated. LTA increased MMP 9 expression and secretion at 12h of treatment. The modulation of MMP 9 secretion was dose dependent, with maximal effect above 1microg/ml. The inhibitor of mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway (U0126, 10microM) prevented LTA stimulation of MMP 9 secretion; however, the inhibitors of p38 (SB203580, 10microM) and Jun N-terminal kinase (JNK; SP600125, 10microM) presented any effect. A2A and A2B adenosine receptors pharmacological blockade or gene knockdown resulted in exacerbated MMP 9 secretion, while an adenosine receptors agonist inhibited LTA-stimulated MMP 9 secretion. These results suggest that LTA increased MMP 9 secretion in macrophages could be involved in complications associated to S. aureus infections. Moreover, LTA modulation of MMP 9 is dependent on MEK/ERK pathway and is regulated by A2A and A2B adenosine receptors. |
| Databáze: | OpenAIRE |
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