Inhibition of Osteoblast Function by Brucella abortus is Reversed by Dehydroepiandrosterone and Involves ERK1/2 and Estrogen Receptor

GENTILINI, MARÍA VIRGINIA; PESCE VIGLIETTI, AYELÉN IVANA; ARRIOLA BENITEZ, PAULA CONSTANZA; IGLESIAS MOLLI, ANDREA ELENA; CERRONE, GLORIA EDITH; GIAMBARTOLOMEI, GUILLERMO HERNÁN; DELPINO, MARÍA VICTORIA

Frontiers in Immunology

Frontiers

Lugar: Lausana; Año: 2018 vol. 9

Brucella abortus induces an inflammatory response that stimulates the endocrine systemresulting in the secretion of cortisol and dehydroepiandrosterone (DHEA). Osteoarticularbrucellosis is the most common presentation of the active disease in humans, and wehave previously demonstrated that B. abortus infection inhibits osteoblast function. Weaimed to evaluate the role of cortisol and DHEA on osteoblast during B. abortus infection.B. abortus infection induces apoptosis and inhibits osteoblast function. DHEA treatmentreversed the effect of B. abortus infection on osteoblast by increasing their proliferation,inhibiting osteoblast apoptosis, and reversing the inhibitory effect of B. abortus on osteoblastdifferentiation and function. By contrast, cortisol increased the effect of B. abortusinfection. Cortisol regulates target genes by binding to the glucocorticoid receptor(GR). B. abortus infection inhibited GRα expression. Cell responses to cortisol not onlydepend on GR expression but also on its intracellular bioavailability, that is, dependenton the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (HSD) type-1,11β-HSD2 (which convert cortisone to cortisol and vice versa, respectively). Alterationsin the expression of these isoenzymes in bone cells are associated with bone loss.B. abortus infection increased 11β-HSD1 expression but had no effect on 11β-HSD2.DHEA reversed the inhibitory effect induced by B. abortus infection on osteoblast matrixdeposition in an estrogen receptor- and ERK1/2-dependent manner. We conclude thatDHEA intervention improves osteoblast function during B. abortus infection making it apotential candidate to ameliorate the osteoarticular symptoms of brucellosis.