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


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.
Sanna
Francesca
F
Dipartimento di Scienze e Tecnologie Biomediche, Sez di Patologia Sperimentale, University of Cagliari, Cagliari, Italy.
Bonatesta
Rosa Rita
RR
Frongia
Bruno
B
Uda
Sabrina
S
Banni
Sebastiano
S
Melis
Maria Paola
MP
Collu
Maria
M
Madeddu
Clelia
C
Serpe
Roberto
R
Puddu
Silvana
S
Porcu
Giovanna
G
Dessì
Sandra
S
Batetta
Barbara
B
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004951:Esterification; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
D015415:Biomarkers; D016207:Cytokines; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D014316:Tritium; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D002784:Cholesterol; D005954:Glucosephosphate Dehydrogenase; D013936:Thymidine