Homocysteine elicits an M1 phenotype in murine macrophages through an EMMPRIN-mediated pathway.
Can J Physiol Pharmacol
; 93(7): 577-84, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-26118387
ABSTRACT
INTRODUCTION:
Hyperhomocysteinemia (HHcy) is associated with inflammatory diseases and is known to increase the production of reactive oxygen species (ROS), matrix metalloproteinase (MMP)-9, and inducible nitric oxide synthase, and to decrease endothelial nitric oxide production. However, the impact of HHcy on macrophage phenotype differentiation is not well-established. It has been documented that macrophages have 2 distinct phenotypes the "classically activated/destructive" (M1), and the "alternatively activated/constructive" (M2) subtypes. We hypothesize that HHcy increases M1 macrophage differentiation through extracellular matrix metalloproteinase inducer (EMMPRIN), a known inducer of matrix metalloproteinases.METHODS:
murine J774A.1 and Raw 264.7 macrophages were treated with 100 and 500 µmol/L Hcy, respectively, for 24 h. Samples were analyzed using Western blotting and immunocytochemistry.RESULTS:
Homocysteine treatment increased cluster of differentiation 40 (CD40; M1 marker) in J774A.1 and Raw 264.7 macrophages. MMP-9 was induced in both cell lines. EMMPRIN protein expression was also increased in both cell lines. Blocking EMMPRIN function by pre-treating cells with anti-EMMPRIN antibody, with or without Hcy, resulted in significantly lower expression of CD40 in both cell lines by comparison with the controls. A DCFDA assay demonstrated increased ROS production in both cell lines with Hcy treatment when compared with the controls.CONCLUSION:
Our results suggest that HHcy results in an increase of the M1 macrophage phenotype. This effect seems to be at least partially mediated by EMMPRIN induction.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Espécies Reativas de Oxigênio
/
Basigina
/
Homocisteína
/
Macrófagos
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article