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 24â¯h with BAY 41-2272 at 3⯵M and 30⯵M, followed by activation with 90â¯nM phorbol myristate acetate (PMA), inhibited interferon-gamma (IFN-γ) production, with 3⯵M and 30⯵M BAY causing 16.5-fold and 12.1-fold inhibition, respectively, compared to PMA alone (pâ¯<â¯0.05, one-way ANOVA followed by Tukey's test). We also observed suppressive effects on the expression of CD69, with 30⯵M BAY causing 3.55-fold lower expression than PMA/ionomycin (pâ¯<â¯0.001 one-way ANOVA followed by Tukey's test), and T-bet, with 30⯵M BAY causing 1.47-fold lower expression than PMA/ionomycin (pâ¯<â¯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⯵M BAY and 30⯵M BAY compared to PMA/ionomycin (pâ¯<â¯0.01, pâ¯<â¯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/farmacologiaRESUMO
Chronic granulomatous disease (CGD) is an innate immune deficiency of phagocytic cells caused by mutations that affect components of the NADPH oxidase system, with resulting impairment in reactive oxygen species production. Patients with CGD are susceptible to recurrent infections and hyperinflammatory responses. Mutations in CYBB lead to the X-linked form of CGD and are responsible for ~ 70% of cases. In this study, we report the case of a 2.5-year-old male patient with recurrent pneumonia and Bacillus Calmette-Guérin infection (BCGitis). As his first clinical manifestation, he presented with bullous impetigo at 18 days of age, which was followed by recurrent pneumonia and regional BCGitis. Genetic analysis revealed a de novo mutation in exon 5 of the CYBB gene: a single-nucleotide substitution, c.376T > C, leading to a C126R change.
RESUMO
The original version of abstract PO-162 "Chronic Granulomatous Disease in a Brazilian Patient Mimetizing Sarcoidosis" incorrectly listed the name of the second author as Micheli Barsioti. The correct spelling of the author's name is Michele Baziotti Man.