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

A. I. PESCE VIGLIETTI, M. V. GENTILINI, P. C. ARRIOLA BENITEZ, A. E. IGLESIAS MOLLI, G. H. GIAMBARTOLOMEI, M. V. DELPINO.

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

Osteoarticular brucellosis is the most frequentcomplication of the active disease.Osteocytes are the most abundant cells of bone, and B. abortus infection modulates osteocyte function. Since bone remodeling process is regulated by hormoneswe decided to study the effect of cortisol and DHEA in B. abortus-infectedosteocytes. Cortisol treatment inhibited the expression of MMP-2, TNF-α, IL-6and RANKL induced by B. abortus infectionin osteocytes. DHEA could only reversethe inhibitory effect of cortisol on MMP-2 production. B. abortus infection reduced connexin (Cx43) expression on osteocytes, aphenomenon that was increased when infection experiments were performed in thepresence of cortisol and it was partially reversed by DHEA treatment. RANKL isthe main cytokine involved in osteoclastogenesis. Supernatants from osteocytes infected with B. abortus induced osteoclastogenesis of osteoclast precursors.Yet, the presence of cortisol, but not DHEA; during osteocyte infectioninhibited the osteoclastogenic effect of the supernatants. Cortisol regulates target genes by binding to theglucocorticoid receptor (GR). B.abortus infection increase GRα/β ratio. The levels of intracellular cortisol are notonly dependent on GR expression but also a result of the activity of theisoenzymes 11β-hydroxysteroiddehydrogenase (11βHSD)-1 (cortisone to cortisol conversion), 11β-HSD2 (cortisol to cortisone conversion). Our data indicated that B. abortus infection increased 11β-HSD1/2. The importance of the increase ofcortisol/cortisone ratio was revealed by the use of cortisone that mimics theeffect of cortisol. Taken together, our data indicate that DHEA treatment mayhave only positive effect in some aspect of osteocyte activity during B. abortus, but not in all of them.