Abstract
Brucella abortus induces an inflammatory response that stimulates the endocrine system resulting in the secretion of cortisol and dehydroepiandrosterone (DHEA). Osteoarticular brucellosis is the most common presentation of the active disease in humans, and we have previously demonstrated that B. abortus infection inhibits osteoblast function. We aimed to evaluate the role of cortisol and DHEA on osteoblast during B. abortus infection. B. abortus infection induces apoptosis and inhibits osteoblast function. DHEA treatment reversed the effect of B. abortus infection on osteoblast by increasing their proliferation, inhibiting osteoblast apoptosis, and reversing the inhibitory effect of B. abortus on osteoblast differentiation and function. By contrast, cortisol increased the effect of B. abortus infection. Cortisol regulates target genes by binding to the glucocorticoid receptor (GR). B. abortus infection inhibited GRα expression. Cell responses to cortisol not only depend on GR expression but also on its intracellular bioavailability, that is, dependent on the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (HSD) type-1, 11β-HSD2 (which convert cortisone to cortisol and vice versa, respectively). Alterations in 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 matrix deposition in an estrogen receptor- and ERK1/2-dependent manner. We conclude that DHEA intervention improves osteoblast function during B. abortus infection making it a potential candidate to ameliorate the osteoarticular symptoms of brucellosis.
Highlights
Brucellosis is primarily a disease of domestic and wild animals that can be transmitted to humans, in whom it affects several organs and tissues, given rise to various clinical manifestations
We decided to evaluate if cortisol and DHEA treatment could modify the capacity of B. abortus to replicate into osteoblast
Taken together these results indicate that cortisol treatment increases intracellular replication and DHEA is able to reverse the effect of cortisol
Summary
Brucellosis is primarily a disease of domestic and wild animals that can be transmitted to humans, in whom it affects several organs and tissues, given rise to various clinical manifestations. Among many stratagems employed by the bacterium to harm bone, Brucella can infect and survive within human and murine osteoblasts, and this infection triggers the secretion of receptor activator of nuclear factor-κB ligand (RANKL), proinflammatory cytokines, and chemokines that could be implicated in the presentation of osteoarticular brucellosis. Such a response is further amplified in the face of B. abortus infection by reciprocal influence between osteoblasts and monocytes [7, 8]
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