Heme oxygenase-1—Dependent anti-inflammatory effects of atorvastatin in zymosan-injected subcutaneous air pouch in mice

Autor: Bassam Badran, Eva Hamade, May F. Mrad, Charbel A. Mouawad, Aida Habib, Ayad A. Jaffa, Ghewa A. El-Achkar, Roberto Motterlini
Přispěvatelé: Department of Biochemistry and Molecular Genetics [Beyrouth, Liban], American University of Beirut [Beyrouth] (AUB), Équipe 12 [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Nehme and Therese Tohme Multiple Sclerosis Center [Beyrouth, Liban] (AUBMC), American University of Beirut Medical Center [Beyrouth, Liban] (AUBMC), American University of Beirut [Beyrouth] (AUB)-American University of Beirut [Beyrouth] (AUB), Laboratory of Cancer Biology and Molecular Immunology [Beyrouth, Liban], Lebanese University [Beirut] (LU), Laboratoire d'Excellence Inflamex [Paris], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), This study has been funded with supports from the National Council for Scientific Research in Lebanon (to AH and EH, 02-05-16), the Medical Practice Plan (MPP to AH), the Faculty of Medicine of the American University of Beirut (to AH), the Ecole Doctorale Des Sciences et Technologie of the Lebanese University (to E.H.), INSERM (To RM), the Université Paris-Est Créteil (to RM)., Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bodescot, Myriam
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Chemokine
Physiology
Atorvastatin
Gene Expression
Pharmacology
Pathology and Laboratory Medicine
Biochemistry
chemistry.chemical_compound
White Blood Cells
0302 clinical medicine
Spectrum Analysis Techniques
Animal Cells
Immune Physiology
Medicine and Health Sciences
Post-Translational Modification
Immune Response
Innate Immune System
Multidisciplinary
biology
Drugs
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
Flow Cytometry
3. Good health
[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences
medicine.anatomical_structure
Spectrophotometry
030220 oncology & carcinogenesis
Medicine
[SDV.IMM]Life Sciences [q-bio]/Immunology
Cytokines
Cytophotometry
medicine.symptom
Cellular Types
Mannose receptor
medicine.drug
Research Article
[SDV.IMM] Life Sciences [q-bio]/Immunology
Science
Immune Cells
Immunology
Inflammation
Heme
Research and Analysis Methods
Proinflammatory cytokine
03 medical and health sciences
Signs and Symptoms
Diagnostic Medicine
medicine
Genetics
Blood Cells
Monocyte
Macrophages
Zymosan
Statins
Biology and Life Sciences
Proteins
Cell Biology
Molecular Development
Heme oxygenase
030104 developmental biology
chemistry
Immune System
biology.protein
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Public Library of Science, 2019, 14 (5), pp.e0216405. ⟨10.1371/journal.pone.0216405⟩
PLoS ONE, Vol 14, Iss 5, p e0216405 (2019)
PLoS ONE, 2019, 14 (5), pp.e0216405. ⟨10.1371/journal.pone.0216405⟩
ISSN: 1932-6203
Popis: International audience; Statins exert pleiotropic and beneficial anti-inflammatory and antioxidant effects. We have previously reported that macrophages treated with statins increased the expression of heme oxygenase-1 (HO-1), an inducible anti-inflammatory and cytoprotective stress protein, responsible for the degradation of heme. In the present study, we investigated the effects of atorvastatin on inflammation in mice and analyzed its mechanism of action in vivo. Air pouches were established in 8 week-old female C57BL/6J mice. Atorvastatin (5 mg/kg, i.p.) and/or tin protoporphyrin IX (SnPPIX), a heme oxygenase inhibitor (12 mg/kg, i.p.), were administered for 10 days. Zymosan, a cell wall component of Saccharomyces cerevisiae, was injected in the air pouch to trigger inflammation. Cell number and levels of inflammatory markers were determined in exudates collected from the pouch 24 hours post zymosan injection by flow cytometry, ELISA and quantitative PCR. Analysis of the mice treated with atorvastatin alone displayed increased expression of HO-1, arginase-1, C-type lectin domain containing 7A, and mannose receptor C-type 1 in the cells of the exudate of the air pouch. Flow cytometry analysis revealed an increase in monocyte/macrophage cells expressing HO-1 and in leukocytes expressing MRC-1 in response to atorvastatin. Mice treated with atorvastatin showed a significant reduction in cell influx in response to zymosan, and in the expression of proinflammatory cytokines and chemokines such as interleukin-1α, monocyte chemoattractant protein-1 and prostaglandin E2. Co-treatment of mice with atorvastatin and tin protoporphyrin IX (SnPPIX), an inhibitor of heme oxygenase, reversed the inhibitory effect of statin on cell influx and proinflammatory markers, suggesting a protective role of HO-1. Flow cytometry analysis of air pouch cell contents revealed prevalence of neutrophils and to a lesser extent of monocytes/macrophages with no significant effect of atorvastatin treatment on the modification of their relative proportion. These findings identify HO-1 as a target for the therapeutic actions of atorvastatin and highlight its potential role as an in vivo anti-inflammatory agent.
Databáze: OpenAIRE
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