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Int Immunopharmacol ; 77: 105976, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31732450

RESUMO

BAY 41-2272 increases guanosine 3', 5'-cyclic monophosphate (cGMP) levels by stimulating soluble guanylate cyclase (sGC). In this study, we evaluated the effect of BAY 41-2272 on human T lymphocyte functions. Pretreating T cells for 24 h with BAY 41-2272 at 3 µM and 30 µM, followed by activation with 90 nM phorbol myristate acetate (PMA), inhibited interferon-gamma (IFN-γ) production, with 3 µM and 30 µM BAY causing 16.5-fold and 12.1-fold inhibition, respectively, compared to PMA alone (p < 0.05, one-way ANOVA followed by Tukey's test). We also observed suppressive effects on the expression of CD69, with 30 µM BAY causing 3.55-fold lower expression than PMA/ionomycin (p < 0.001 one-way ANOVA followed by Tukey's test), and T-bet, with 30 µM BAY causing 1.47-fold lower expression than PMA/ionomycin (p < 0.05, one-way ANOVA test followed by Tukey's test). Additionally, T lymphocyte proliferation was reduced 2.13-fold and 4.3-fold, respectively, by 3 µM BAY and 30 µM BAY compared to PMA/ionomycin (p < 0.01, p < 0.001, one-way ANOVA followed by Tukey's test). BAY 41-2272 inhibits human T lymphocyte function and may be explored as an immunomodulatory drug in patients with autoimmune/inflammatory diseases and lymphoproliferative syndromes.


Assuntos
Pirazóis/farmacologia , Piridinas/farmacologia , Linfócitos T/efeitos dos fármacos , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Proliferação de Células/efeitos dos fármacos , Guanilato Ciclase/metabolismo , Humanos , Fatores Imunológicos/metabolismo , Interferon gama/metabolismo , Ionomicina/farmacologia , Lectinas Tipo C/metabolismo , Linfócitos T/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
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