TY - JOUR

T1 - Production of inflammatory molecules in peripheral blood mononuclear cells from severely glucose-6-phosphate dehydrogenase-deficient subjects.

AU - Sanna, Francesca

AU - Bonatesta, Rosa Rita

AU - Frongia, Bruno

AU - Uda, Sabrina

AU - Banni, Sebastiano

AU - Melis, Maria Paola

AU - Collu, Maria

AU - Madeddu, Clelia

AU - Serpe, Roberto

AU - Puddu, Silvana

AU - Porcu, Giovanna

AU - Dessì, Sandra

AU - Batetta, Barbara

N1 - Keywords: Adult; Biological Markers; Cells, Cultured; Cholesterol; Cytokines; Esterification; Fatty Acids, Unsaturated; Foam Cells; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Humans; Hydroxyeicosatetraenoic Acids; Leukocytes, Mononuclear; Macrophages; Male; Monocytes; Severity of Illness Index; Thymidine; Tritium

PY - 2007

Y1 - 2007

N2 - OBJECTIVE: We have previously demonstrated that Mediterranean glucose-6-phosphate dehydrogenase (G6PD)-deficient peripheral blood mononuclear cells (PBMC) respond to mitogenic stimuli with a reduced cholesterol synthesis and growth. In the present study, we have investigated the release of inflammatory molecules by PBMC following a mitogenic stimulus, as well as the transformation to foam cells of monocyte-derived macrophages from severely G6PD-deficient and normal subjects. METHODS AND RESULTS: PBMC from G6PD-deficient subjects produced interleukin (IL)-1beta and IL-6 to a lower extent compared with normal subjects. 5-Hydroxyeicosatetraenoic acid, a primary product of 5-lipoxygenase, was slightly decreased. Tumour necrosis factor-alpha and IL-1beta secretion was significantly reduced in monocyte-derived macrophages. No difference was found in IL-10 secretion, whereas transforming growth factor-beta was invariably found to be significantly higher in G6PD-deficient cells. In cells incubated with acetylated low-density lipoprotein, cholesterol esterification and its storage in lipid droplets were lower than in normal G6PD cells. CONCLUSIONS: We conclude that by reducing the secretion of inflammatory molecules by PBMC and increasing the secretion of transforming growth factor-beta and the capability of monocyte-derived macrophages to accumulate lipid droplets and convert into foam cells, G6PD deficiency may confer a partial protection against atherosclerosis leading to the reduced risk of cardiovascular diseases reported in G6PD-deficient subjects.

AB - OBJECTIVE: We have previously demonstrated that Mediterranean glucose-6-phosphate dehydrogenase (G6PD)-deficient peripheral blood mononuclear cells (PBMC) respond to mitogenic stimuli with a reduced cholesterol synthesis and growth. In the present study, we have investigated the release of inflammatory molecules by PBMC following a mitogenic stimulus, as well as the transformation to foam cells of monocyte-derived macrophages from severely G6PD-deficient and normal subjects. METHODS AND RESULTS: PBMC from G6PD-deficient subjects produced interleukin (IL)-1beta and IL-6 to a lower extent compared with normal subjects. 5-Hydroxyeicosatetraenoic acid, a primary product of 5-lipoxygenase, was slightly decreased. Tumour necrosis factor-alpha and IL-1beta secretion was significantly reduced in monocyte-derived macrophages. No difference was found in IL-10 secretion, whereas transforming growth factor-beta was invariably found to be significantly higher in G6PD-deficient cells. In cells incubated with acetylated low-density lipoprotein, cholesterol esterification and its storage in lipid droplets were lower than in normal G6PD cells. CONCLUSIONS: We conclude that by reducing the secretion of inflammatory molecules by PBMC and increasing the secretion of transforming growth factor-beta and the capability of monocyte-derived macrophages to accumulate lipid droplets and convert into foam cells, G6PD deficiency may confer a partial protection against atherosclerosis leading to the reduced risk of cardiovascular diseases reported in G6PD-deficient subjects.

U2 - 10.1159/000100903

DO - 10.1159/000100903

M3 - Journal article

C2 - 17361089

VL - 44

SP - 253

EP - 263

JO - Journal of Vascular Research

JF - Journal of Vascular Research

SN - 1018-1172

IS - 4

ER -