Immune endocrine modulation of osteocytes responses during B. abortus infection.

AYELEN IVANA PESCE VIGLIETTI ; MARÍA VIRGINIA GENTILINI; PAULA CONSTANZA ARRIOLA BENITEZ; ANDREA ELENA IGLESIAS MOLLI; GUILLERMO HERNAN GIAMBARTOLOMEI; MARÍA VICTORIA DELPINO

Buenos Aires

Congreso; Reunión Conjunta de Biociencias 2017.; 2017

Patients with brucellosis have an imbalance in cortisol/ DHEA ratio in plasma. Bone remodeling process is regulated by hormones. Then, we aimed to study the effect of cortisol and DHEA on osteocytes (the most abundant cells of bone) during B. abortus (Ba) infection. Cortisol treatment inhibited the expression of TNF-α, IL-6 and RANKL (the main regulator of osteoclastogenesis) induced by Ba infection (p<0.001, ELISA). DHEA reversed the effect of cortisol on TNF-α expression, but not on the expression of IL-6 and RANKL during Ba infection. Ba infection induced MMP-2 by osteocytes (zymography). When cortisol was added during Ba infection the secretion of MMP-2 was inhibited. When the infection experiments were performed in the presence of both cortisol and DHEA, DHEA could reverse the inhibitory effect of cortisol on MMP-2 production. RANKL and TNF-α are the main cytokines involved in osteoclastogenesisin inflammatory conditions. We performed osteoclastogenesis experiments by added supernatants from osteocytes infected with Ba in the presence of cortisol and DHEA to osteoclastprecursors (RAW 264.7) in the presence of M-CSF. Our results indicated that cortisol inhibit the osteoclastogenesis induced by supernatants from Ba infected osteocytes (p<0.001, TRAP staining). It is known that cortisol regulates target genes by binding to the glucocorticoid receptor (GR). Ba infection inhibited GR-α and GR-β expression (p<0.01, RT-qPCR).The levels of intracellular cortisol is not only dependent on GR expression but also a result of the activity of the isoenzymes 11β-HSD1 (cortisone to cortisol conversion), 11β-HSD2 (cortisol to cortisone). Ba infection increased 11β-HSD1 expression (p<0.05) and inhibited 11β-HSD2 expression by osteocytes (p<0.001, RT-qPCR). The present study constitutes the first analysis on the immune-endocrine alterations in osteocytes during Ba infection and providesan initial background for studying in more detail the role of DHEAduring the infection.