Opposite effects of simvastatin on the bactericidal and inflammatory response of macrophages to opsonized S. aureus
| Autor: | Daniela Benati, Micol Ferro, Cosima T. Baldari, Franco Laghi Pasini, Maria Teresa Savino, Annalisa Nuccitelli, Cristina Ulivieri, Ebe Schiavo |
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| Rok vydání: | 2009 |
| Předmět: |
rho GTP-Binding Proteins
Simvastatin Staphylococcus aureus statins macrophage phagocytosis proinflammatory cytokines signal transduction immunosuppression Phagocytosis Immunology Protein Prenylation Inflammation Context (language use) Fc receptors Oxidative burst Protein prenylation Ras superfamily GTpases Statins Actins Animals Cell Line Cytoskeleton Humans Inflammation Mediators Macrophages Membrane Microdomains Mice Microbial Viability Opsonin Proteins Receptors IgG Respiratory Burst Signal Transduction ras Proteins Cell Biology Biology Proinflammatory cytokine medicine Immunology and Allergy Macrophage nutritional and metabolic diseases Respiratory burst lipids (amino acids peptides and proteins) medicine.symptom medicine.drug |
| Zdroj: | Journal of leukocyte biology. 87(3) |
| ISSN: | 1938-3673 |
| Popis: | By impairing prenylation of Ras-related GTPases, simvastatin blocks phagocytosis and oxidative burst while enhancing production of proinflammatory mediators in human macrophages challenged with IgG-coated bacteria. Besides lowering circulating cholesterol, statins act as immunomodulators. Although the effects of statins on lymphocyte activation and differentiation have been clearly defined, there is no consensus as to effects of these drugs on phagocytes. We have addressed the outcome of simvastatin treatment on the activation and effector function of human macrophages in the pathophysiologically relevant context of challenge with an opportunistic pathogen. We provide evidence that: simvastatin blocks the biological effects rapidly triggered by IgG-opsonized bacteria (phagocytosis and oxidative burst) while enhancing the delayed effects elicited by FcγR stimulation (production of proinflammatory mediators); these opposite effects of simvastatin result from enhancement of the JNK pathway and concomitant impairment of other signaling modules activated by FcγR engagement; and these activities are dependent on the capacity of simvastatin to block protein prenylation. The results provide novel mechanistic insight into the activities of statins on phagocytes and are of relevance to the assessment of potential side-effects in patients undergoing long-term hypocholesterolemic therapy. |
| Databáze: | OpenAIRE |
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