Pathological concentrations of homocysteine increases IL-1β production in macrophages in a P2X7, NF-ĸB, and erk-dependent manner.

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-1β. 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-1β, and the advance of vascular diseases. The purpose of the present study is to investigate the effects of Hcy on IL-1β secretion by murine macrophages. Hcy (100 μM) increases IL-1β 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-1β 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-1β via NF-ĸB, ERK, and P2X7 stimulation in murine macrophages.

• Authors: Rafael Fernandes Zanin, Letícia Scussel Bergamin, Fernanda Bueno Morrone, Robson Coutinho-Silva, Angela Terezinha de Souza Wyse, Ana Maria Oliveira Battastini
• Journal: Purinergic signalling (Purinergic Signal) Vol. 11 Issue 4 Pg. 463-70 (Dec 2015) ISSN: 1573-9546 [Electronic] Netherlands
• PMID: 26265456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• IL1B protein, mouse
• Interleukin-1beta
• NF-kappa B
• Reactive Oxygen Species
• Receptors, Purinergic P2X7
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Homocysteine
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Homocysteine (toxicity)
• Hyperhomocysteinemia (metabolism)
• Interleukin-1beta (biosynthesis)
• MAP Kinase Signaling System (drug effects)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NF-kappa B (metabolism)
• Reactive Oxygen Species (metabolism)
• Receptors, Purinergic P2X7 (metabolism)
• Toll-Like Receptor 4 (genetics)