Anti-inflammatory effect of fluvastatin on IL-8 production induced by Pseudomonas aeruginosa and Aspergillus fumigatus antigens in cystic fibrosis
| Autor: | G. Brinchault, Benoit Desrues, Jeanne Galaine, Mélanie Bonizec, Chantal Belleguic, Stéphane Jouneau, Corinne Martin-Chouly, Jean-Pierre Gangneux |
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| Přispěvatelé: | Service de pneumologie, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Service de Parasitologie-Mycologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], 'Vaincre la mucoviscidose', le Conseil scientifique de la Faculté de Médecine de l'Université de Rennes 1, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes] |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Pulmonology Pharmacology MESH: Terpenes Aspergillus fumigatus 0302 clinical medicine MESH: Indoles 0303 health sciences Clinical Pharmacology MESH: Case-Control Studies 3. Good health MESH: Young Adult [SDV.TOX]Life Sciences [q-bio]/Toxicology Cytokines Medicine Antigens Fungal Science Immunology Mevalonic Acid Mevalonic acid Microbiology 03 medical and health sciences Inhibitory Concentration 50 Genetics Humans Aspergillosis Pseudomonas Infections Biology MESH: Antigens Fungal MESH: Adolescent MESH: Humans Immunity MESH: Adult Molecular Development MESH: Interleukin-8 030228 respiratory system chemistry Pharmacodynamics Case-Control Studies MESH: Anti-Inflammatory Agents Mutation MESH: Lipopolysaccharides MESH: Female Developmental Biology Lipopolysaccharides Bacterial Diseases Chemokine Indoles Anatomy and Physiology Cystic Fibrosis Anti-Inflammatory Agents Cystic Fibrosis Transmembrane Conductance Regulator medicine.disease_cause Fatty Acids Monounsaturated chemistry.chemical_compound Autosomal Recessive Immune Physiology Whole blood MESH: Inhibitory Concentration 50 MESH: Cystic Fibrosis Transmembrane Conductance Regulator Multidisciplinary biology Fungal Diseases MESH: Mevalonic Acid MESH: Fatty Acids Monounsaturated Infectious Diseases Pseudomonas aeruginosa MESH: Pseudomonas aeruginosa Female medicine.symptom MESH: Aspergillus fumigatus medicine.drug Research Article Adult Drugs and Devices MESH: Mutation Adolescent MESH: Cystic Fibrosis Clinical Research Design Preclinical Models Inflammation Young Adult medicine Interleukin 8 Fluvastatin 030304 developmental biology Clinical Genetics Terpenes Interleukin-8 Human Genetics biology.organism_classification MESH: Male Immune System biology.protein Clinical Immunology |
| Zdroj: | PLoS ONE, Vol 6, Iss 8, p e22655 (2011) PLoS ONE PLoS ONE, 2011, 6 (8), pp.e22655. ⟨10.1371/journal.pone.0022655⟩ PLoS ONE, Public Library of Science, 2011, 6 (8), pp.e22655. ⟨10.1371/journal.pone.0022655⟩ |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0022655⟩ |
| Popis: | International audience; BACKGROUND: Early in life, patients with cystic fibrosis (CF) are infected with microorganisms including bacteria and fungi, particularly Pseudomonas aeruginosa and Aspergillus fumigatus. Since recent research has identified the anti-inflammatory properties of statins (besides their lipid-lowering effects), we investigated the effect of fluvastatin on the production of the potent neutrophil chemoattractant chemokine, IL-8, in whole blood from CF patients, stimulated by Pseudomonas aeruginosa (LPS) and Aspergillus fumigatus (AFA) antigens. RESULTS: Whole blood from adult patients with CF and from healthy volunteers was collected at the Rennes University Hospital (France). Blood was pretreated for 1 h with fluvastatin (0-300 µM) and incubated for 24 h with LPS (10 µg/mL) and/or AFA (diluted 1/200). IL-8 protein levels, quantified by ELISA, were increased in a concentration-dependent manner when cells were stimulated by LPS or AFA. Fluvastatin strongly decreased the levels of IL-8, in a concentration-dependent manner, in whole blood from CF patients. However, its inhibitory effect was decreased or absent in whole blood from healthy subjects. Furthermore, the inhibition induced by fluvastatin in CF whole blood was reversed in the presence of intermediates within the cholesterol biosynthesis pathway, mevalonate, farnesyl pyprophosphate or geranylgeranyl pyrophosphate that activate small GTPases by isoprenylation. CONCLUSIONS: For the first time, the inhibitory effects of fluvastatin on CF systemic inflammation may reveal the important therapeutic potential of statins in pathological conditions associated with the over-production of pro-inflammatory cytokines and chemokines as observed during the manifestation of CF. The anti-inflammatory effect could be related to the modulation of the prenylation of signalling proteins. |
| Databáze: | OpenAIRE |
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