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

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

Publication date: Nov 20, 2018

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.

Open Access PDF

El-Achkar, G.A., Mrad, M.F., Mouawad, C.A., Badran, B., Jaffa, A.A., Motterlini, R., Hamade, E., and Habib, A. Heme oxygenase-1-Dependent anti-inflammatory effects of atorvastatin in zymosan-injected subcutaneous air pouch in mice. 17961. 2018 PLoS One (14):5.

Concepts Keywords
Air Monocyte
Antioxidant Heme oxygenase
Atorvastatin Atorvastatin
Chemoattractant Macrophage
Chemokines HMOX1
Cytokines Diols
ELISA Zymosan
Exudate Carbon monoxide
Flow Cytometry Immune system
Heme Cytokines
Inflammation Cell biology
Inhibitor Branches of biology
Interleukin 1 Atorvastatin inflammation
Lectin
Leukocytes
Macrophage
Macrophages
Mannose
Mice
Monocyte
Monocytes
Neutrophils
Oxygenase
Pleiotropic
Prostaglandin E2
Protein
Protoporphyrin
Quantitative PCR
Receptor
Saccharomyces Cerevisiae
Statin
Statins
Stress
Subcutaneous
Tin
Vivo

Semantics

Type Source Name
gene UNIPROT ITGAM
gene UNIPROT PTPRC
disease MESH multi
gene UNIPROT GCA
gene UNIPROT NOS2
gene UNIPROT NANOS2
gene UNIPROT PTGS2
gene UNIPROT MIXL1
gene UNIPROT KIT
gene UNIPROT C2
drug DRUGBANK Isoflurane
drug DRUGBANK Coenzyme M
gene UNIPROT LRRC15
drug DRUGBANK Water
gene UNIPROT TNFSF14
gene UNIPROT MENT
drug DRUGBANK Trestolone
gene UNIPROT DDX53
gene UNIPROT NAA50
disease MESH tumor
gene UNIPROT TNF
gene UNIPROT PTGES
gene UNIPROT MRC1
gene UNIPROT CAPG
gene UNIPROT CD46
gene UNIPROT CLEC7A
gene UNIPROT ARG1
gene UNIPROT TINAGL1
drug DRUGBANK Dimethyl sulfoxide
gene UNIPROT ARSA
drug DRUGBANK Acetylsalicylic acid
gene UNIPROT COX5A
gene UNIPROT COX8A
gene UNIPROT CPOX
gene UNIPROT HMGA2
disease MESH Multiple
drug DRUGBANK Nitric Oxide
gene UNIPROT IRF6
drug DRUGBANK Cholesterol
gene UNIPROT DES
drug DRUGBANK Diethylstilbestrol
gene UNIPROT MPZ
gene UNIPROT MPHOSPH6
gene UNIPROT TNFSF13
gene UNIPROT ANP32B
gene UNIPROT ERBB2
gene UNIPROT NEU1
gene UNIPROT NEURL1
gene UNIPROT ABCC8
disease DOID Multiple Sclerosis
disease MESH Multiple Sclerosis
gene UNIPROT SULT1E1
gene UNIPROT MAP3K8
gene UNIPROT ZNF746
gene UNIPROT AIDA
gene UNIPROT ANKS1B
gene UNIPROT MPZL2
gene UNIPROT SLC26A4
drug DRUGBANK Dinoprostone
gene UNIPROT CD200
drug DRUGBANK Mannose
gene UNIPROT SLC35G1
drug DRUGBANK Protoporphyrin
disease MESH inflammation
gene UNIPROT HMOX1
drug DRUGBANK Medical air
drug DRUGBANK Atorvastatin

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *