Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Inhibition of Osteoblast Function by Brucella abortus is Reversed by Dehydroepiandrosterone and Involves ERK1/2 and Estrogen Receptor
Ist Teil von
Frontiers in immunology, 2018-01, Vol.9, p.88-88
Ort / Verlag
Switzerland: Frontiers Research Foundation
Erscheinungsjahr
2018
Link zum Volltext
Quelle
Elektronische Zeitschriftenbibliothek
Beschreibungen/Notizen
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
infection inhibits osteoblast function. We aimed to evaluate the role of cortisol and DHEA on osteoblast during
infection.
infection induces apoptosis and inhibits osteoblast function. DHEA treatment reversed the effect of
infection on osteoblast by increasing their proliferation, inhibiting osteoblast apoptosis, and reversing the inhibitory effect of
on osteoblast differentiation and function. By contrast, cortisol increased the effect of
infection. Cortisol regulates target genes by binding to the glucocorticoid receptor (GR).
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
, respectively). Alterations in the expression of these isoenzymes in bone cells are associated with bone loss.
infection increased 11β-HSD1 expression but had no effect on 11β-HSD2. DHEA reversed the inhibitory effect induced by
infection on osteoblast matrix deposition in an estrogen receptor- and ERK1/2-dependent manner. We conclude that DHEA intervention improves osteoblast function during
infection making it a potential candidate to ameliorate the osteoarticular symptoms of brucellosis.