Pathological concentrations of homocysteine increases IL-1ß production in macrophages in a P2X7, NF-ĸB, and erk-dependent manner.
Purinergic Signal
; 11(4): 463-70, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26265456
ABSTRACT
Elevated plasma levels of homocysteine (Hcy) are associated with the development of coronary artery disease (CAD), peripheral vascular disease, and atherosclerosis. Hyperhomocysteinemia is likely related to the enhanced production of pro-inflammatory cytokines including IL-1ß. However, the mechanisms underlying the effects of Hcy in immune cells are not completely understood. Recent studies have established a link between macrophage accumulation, cytokine IL-1ß, and the advance of vascular diseases. The purpose of the present study is to investigate the effects of Hcy on IL-1ß secretion by murine macrophages. Hcy (100 µM) increases IL-1ß synthesis via enhancement of P2X7 expression and NF-ĸB and ERK activation in murine macrophages. In addition, the antioxidant agent N-acetylcysteine (NAC) reduces NF-κB activation, ERK phosphorylation, and IL-1ß production in Hcy-exposed macrophages, indicating the importance of ROS in this pro-inflammatory process. In summary, our results show that Hcy may be involved in the synthesis and secretion of IL-1ß via NF-ĸB, ERK, and P2X7 stimulation in murine macrophages.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
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Hiper-Homocisteinemia
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Sistema de Sinalização das MAP Quinases
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Interleucina-1beta
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Receptores Purinérgicos P2X7
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Homocisteína
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Macrófagos
Limite:
Animals
Idioma:
En
Revista:
Purinergic Signal
Ano de publicação:
2015
Tipo de documento:
Article