RESUMO
Osteoarticular brucellosis is the most frequent complication of active disease. A large amount of cells in bone are osteocytes. Since bone remodeling process is regulated by hormones we sought to study the effect of cortisol and DHEA in Brucella abortus-infected osteocytes. Cortisol treatment inhibited the expression of IL-6, TNF-α, MMP-2 and RANKL in B. abortus-infected osteocytes. DHEA could reverse the inhibitory effect of cortisol on MMP-2 production. B. abortus infection inhibited connexin 43 (Cx43) expression in osteocytes. This expression was increased when cortisol was incorporated during the infection and DHEA treatment partially reversed the effect of cortisol. Osteocytes-infected with B. abortus induced osteoclast's differentiation. Yet, the presence of cortisol, but not DHEA, during osteocyte infection inhibited osteoclastogenesis. Glucocorticoid receptor (GR) is implicated in the signaling of cortisol. Infection with B. abortus was able to increase GRα/ß ratio. Levels of intracellular cortisol are not only dependent on GR expression but also a result of the activity of the isoenzymes 11ß-hydroxysteroid dehydrogenase (11ß-HSD)-1 (cortisone to cortisol conversion), 11ß-HSD2 (cortisol to cortisone conversion). B. abortus infection increased 11ß-HSD 1/2 ratio and cortisone mimicked the effect of cortisol. Our results indicated that cortisol and DHEA could modulate osteocyte responses during B. abortus infection.
Assuntos
Brucella abortus/fisiologia , Brucelose/patologia , Osteócitos/microbiologia , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , 11-beta-Hidroxiesteroide Desidrogenases/genética , Animais , Brucella abortus/crescimento & desenvolvimento , Brucella abortus/metabolismo , Brucelose/metabolismo , Células Cultivadas , Conexina 43/metabolismo , Cortisona/farmacologia , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Desidroepiandrosterona/farmacologia , Hidrocortisona/metabolismo , Hidrocortisona/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Viabilidade Microbiana , Osteócitos/citologia , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Osteogênese/efeitos dos fármacos , Osteoprotegerina/antagonistas & inibidores , Receptores de Glucocorticoides/genética , Transdução de SinaisRESUMO
The knowledge of the genetic bases of hypertension has improved over the last decade; this area of research has high priority due to the high incidence of hypertension and its impact on public health. Monogenetic mineralocorticoid hypertension syndromes are associated with suppressed plasma renin activity due to excessive activation of the mineralocorticoid pathway. We review the pathophysiology, phenotype, and method of diagnosis for familial hyperaldosteronism type I and type II, hypertensive forms of congenital adrenal hyperplasia, 11beta-hydroxysteroid dehydrogenase type 2 deficiency, Liddle's syndrome, an activating mutation of the MR, and glucocorticoid resistance. We also review some genes that could contribute to essential hypertension.
Assuntos
Hipertensão/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , 11-beta-Hidroxiesteroide Desidrogenases/deficiência , 11-beta-Hidroxiesteroide Desidrogenases/genética , Hiperplasia Suprarrenal Congênita/genética , Angiotensinogênio/genética , Resistência a Medicamentos/fisiologia , Canais Epiteliais de Sódio/genética , Glucocorticoides/fisiologia , Humanos , Hiperaldosteronismo/genética , Síndrome de Excesso Aparente de Minerolocorticoides/fisiopatologia , Peptidil Dipeptidase A/genética , Fenótipo , Receptor Tipo 1 de Angiotensina/genética , Receptores de Mineralocorticoides/genética , SíndromeRESUMO
BACKGROUND: 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme catalyzes interconversion of inactive cortisone to active cortisol. Its expression in adipose tissue has been associated with obesity and some of its metabolic disorders. Controversies regarding which fat depots [subcutaneous adipose tissue (SAT) or visceral adipose tissue (VAT)] have higher expression still remain. The aim of this work was to evaluate 11beta-HSD1 expression in SAT and VAT of obese patients and evaluate its association to metabolic features of metabolic syndrome. METHODS: In 32 morbidly obese patients, paired samples of SAT and VAT were collected. All patients, 40.2+/-12.3 years and 36.7+/-3.8 body mass index (BMI), underwent sleeve gastrectomy or laparoscopic gastric bypass. Gene expression of 11beta-HSD1 in adipose tissue samples were determined by real-time reverse transcriptase polymerase chain reaction. Spearman correlation test was used to evaluate relationships between 11beta-HSD1 levels and clinical and biochemical parameters. RESULTS: 11beta-HSD1 mRNA levels were higher in SAT than in VAT, with median expression levels of 11.4 arbitrary units (AU) and 7.8 AU, respectively (p=0.03). SAT 11beta-HSD1 mRNA were correlated with VAT mRNA levels (r=-0.6, p=0.018) and hip circumference (r=0.66, p=0.018). SAT 11beta-HSD1 levels increase parallel according to BMI category. We did not find a correlation between SAT or VAT with fasting glucose (r=0.15, p=NS), total cholesterol (r=0.13, p=NS), triglycerides (r=0.04, p=NS), and high-density lipoprotein (r=-0.16, p=NS). However, SAT expression in patients with features of MS was higher than those without features of MS. CONCLUSIONS: Our results demonstrate that SATs express higher 11beta-HSD1 mRNA levels than VAT. This finding highlights the importance of SAT in obesity and its possible role on metabolic disorders associated with obesity.