Adrenal steroids modúlate osteoblast funciton during Brucella abortus infection.

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

Congreso; Reunión Conjunta de Biociencias 2017.; 2017

(072) ADRENAL STEROIDS MODULATE OSTEOBLASTFUNCTION DURING Brucella abortus INFECTIONMaria Virginia Gentilini, Ayelén Ivana Pesce Viglietti, PaulaConstanza Arriola Viglietti, Andrea Elena Iglesias Molli, GloriaEdith Cerrone, Guillermo Hernan Giambartolomei, MariaVictoria DelpinoINIGEMBrucella abortus (Ba) induces an inflammatory response that stimulatesthe endocrine system resulting in the secretion of cortisol anddehydroepiandrosterone (DHEA). Osteoarticular brucellosis is themost common presentation of the active disease in humans and wehave previously demonstrated that Ba infection inhibits osteoblastfunction. We aimed to evaluate the role of cortisol and DHEA on osteoblast(MC3T3-E1) during Ba infection. Our results indicated thatDHEA treatment reversed the effect of Ba infection on osteoblast byincreasing the proliferation (BrDU, CSFE), cell viability (MTT) andinhibiting osteoblast apoptosis (Annexin V, TUNEL & Hoechst). Incontrast, cortisol increased the effect of Ba infection. DHEA, also,reversed the inhibitory effect induced by Ba infection on osteoblastmatrix deposition (Alizarin & Sirius Red staining) in an estrogen receptor(antagonist fulvestrant) and ERK1/2 (specific inhibitor It isknown that cortisol regulates target genes by binding to the glucocorticoidreceptor (GR). Ba infection inhibited GR-α and this effectcould not be reversed by cortisol or DHEA treatment. Ba did notinduce changes in the expression of GR-β. Besides, the capacity ofcells to respond to cortisol not only is dependent on GR expressionbut also on its intracellular bioavailability. The levels of intracellularcortisol is a result of the activity of the isoenzymes 11β-HSD1 (cortisoneto cortisol conversion), 11β-HSD2 (cortisol to cortisone). Alterationsin the expression of these isoenzymes in bone cells are associatedwith bone loss. Our data showed that Ba infection increased11β-HSD1 expression. Cortisol treatment inhibited the 11β-HSD1expression induced by Ba. DHEA treatment had no effect. Ba infectiondid not induce changes in expression of 11β-HSD2.We conclude that DHEA intervention improve osteoblast functionduring Ba infection. Thus, DHEA could be considered as a newtreatment against osteoarticular brucellosis.Keywords: Brucella abortus, bone, DHEA, cortisol