title: Folate deficiency enhances the inflammatory response of macrophages.
abstract: B-vitamin deficiency is a risk factor for vascular disease. The mechanism by which the deficiency impacts on disease risk is unclear. We have analysed whether the inflammatory response of mononuclear cells can be modified by cellular folate status in vitro. We show that the mouse monocyte cell line RAW264.7 grown under folate restriction displays a decrease in intracellular folate levels and a reduced growth rate. The cells also show a 2- to 3-fold increase in expression of the inflammatory mediators, IL1β, IL6, TNFα and MCP1 at the RNA and protein level (p<0.01) under conditions of folate deficiency. In contrast the production of the vaso-protective mediator nitric oxide is significantly reduced under these conditions. These metabolic changes are independent of the concentration of homocysteine in the medium and occur in the absence of significant changes in global DNA methylation. Folate deficiency may therefore exacerbate cardiovascular disease by augmenting pro-inflammatory signals in the monocyte-macrophage lineage.
authors.affiliation: Metabolic Health Group, Obesity and Metabolic Health Theme, Rowett Institute of Nutrition & Health, University of Aberdeen, UK. a.kolb@abdn.ac.uk
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Kolb
authors.forename: Linda
authors.initials: L
authors.lastname: Petrie
mesh_terms: D000818:Animals; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019175:DNA Methylation; D005492:Folic Acid / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis
chemical_list: D003470:Culture Media; D016207:Cytokines; D018836:Inflammation Mediators; D009569:Nitric Oxide; D005492:Folic Acid