Effect of HMG-CoA reductase inhibitors on activation of human gammadeltaT cells induced by Mycobacterium tuberculosis antigens.
Lipid rafts are cholesterol-enriched microdomains which act as a platform for the initiation of T-cell activation. To investigate effect of endogenous cholesterol on lipid rafts formation and activation of gammadeltaT cells, human peripheral blood mononuclear cells were stimulated in vitro with Mycobacterium tuberculosis antigens (Mtb-Ag). Lovastatin and fluvastatin, two 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) inhibitors, were used to block endogenous cholesterol biosynthesis. The expression of ganglioside GM1 (GM1), a lipid rafts marker, and CD69, an activation marker, and the level of tyrosine phosphorylation in gammadeltaT cells were measured by flow cytometry. The expression and aggregation of GM1 were also detected with laser confocal microscopy. We found that lovastatin and fluvastatin could obviously inhibit tyrosine phosphorylation and expression of GM1 and CD69 in gammadeltaT cells induced by Mtb-Ag. These results collectively indicated that HMGCR inhibitors might interfere with the formation of lipid rafts and inhibit the activation of gammadeltaT cells induced by Mtb-Ag.
Lü
He-Zuo
HZ
Department of Immunology, Bengbu Medical College, and Anhui Key Laboratory of Infection and Immunity at Bengbu Medical College, Bengbu, People's Republic of China.
Li
Bai-Qing
BQ
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002784:Cholesterol / Q000276:immunology; D005229:Fatty Acids, Monounsaturated / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D005677:G(M1) Ganglioside / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000276:immunology / Q000494:pharmacology*; D007211:Indoles / Q000276:immunology / Q000494:pharmacology*; D037181:Lectins, C-Type; D008148:Lovastatin / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D021962:Membrane Microdomains / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002784:Cholesterol; D005229:Fatty Acids, Monounsaturated; D000077340:Fluvastatin; D005677:G(M1) Ganglioside; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D037181:Lectins, C-Type; D008148:Lovastatin; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000099192:CD69 Antigens