Role of nitric oxide and CCAAT/enhancer-binding protein transcription factor in statin-dependent induction of heme oxygenase-1 in mouse macrophages

Mouawad, Charbel A., Mrad, May F., Al-Hariri, Moustafa, Soussi, Hiba, Hamade, Eva, Alam, Jawed and Habib, Aida (2013) Role of nitric oxide and CCAAT/enhancer-binding protein transcription factor in statin-dependent induction of heme oxygenase-1 in mouse macrophages. PloS One, 8 5: . doi:10.1371/journal.pone.0064092


Author Mouawad, Charbel A.
Mrad, May F.
Al-Hariri, Moustafa
Soussi, Hiba
Hamade, Eva
Alam, Jawed
Habib, Aida
Title Role of nitric oxide and CCAAT/enhancer-binding protein transcription factor in statin-dependent induction of heme oxygenase-1 in mouse macrophages
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-05-22
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0064092
Open Access Status DOI
Volume 8
Issue 5
Total pages 8
Place of publication San Francisco, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted abstract
The effect of statins on heme oxygenase-1 (HO-1) was compared in 2 murine cell lines, RAW 264.7 and J774A.1 cell lines, and in primary peritoneal macrophages of BALB/c or C57BL/6 mice. The role of endogenous nitric oxide and the type of transcription factors involved were explored. Simvastatin and fluvastatin induced HO-1. Pretreatment of cells with l-NMMA or 1400 W, two different nitric oxide synthase inhibitors, partially blocked statin-dependent induction of HO-1 in RAW 264.7 and J774A.1 but not in primary peritoneal macrophages. Induction of HO-1 by statins was dependent on p-38 MAP kinase activation in all types of macrophages. In RAW 264.7 cells, both statins increased the activity of reporter genes linked to the proximal 1.3 kbp promoter of HO-1 (EC50 of 1.4±0.3 µM for simvastatin and 0.6±0.03 µM for fluvastatin). This effect was significantly blocked by 1400 W (80±5.2% inhibition, p<0.02) and mevalonate, the direct metabolite of HMGCoA reductase. Gel retardation experiments implicated C/EBPβ, AP-1 but not USF, for both RAW 264.7 and primary peritoneal macrophages of C57BL/6 mice. Collectively we showed a differential role of endogenous nitric oxide between macrophage cell lines and primary macrophages and an effect of statins in the protection against inflammation by increasing HO-1 expression.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number e64092

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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