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Abstract
Brucella abortus stimulates an inflammatory immune response that stimulates the endocrine system, inducing the secretion of dehydroepiandrosterone (DHEA) and cortisol. In humans, the active disease is generally present as osteoarticular brucellosis. In previous studies we showed that B. abortus infection of synoviocytes creates a proinflammatory microenvironment. We proposed to determine the role of cortisol and DHEA on synoviocytes and infiltrating monocytes during B. abortus infection. Cortisol inhibited IL-6, IL-8, MCP-1, and MMP-2 secretion induced by B. abortus infection in synovial fibroblast. Cortisol-mediated MMP-2 inhibition during B. abortus infection was reversed by IL-6. DHEA inhibited B. abortus-induced RANKL up-regulation in synovial fibroblast through estrogen receptor (ER). B. abortus infection did not modulate glucocorticoid receptor (GR) expression. Cell responses to cortisol also depended on its intracellular bioavailability, according to the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (HSD) type-1 and 11β-HSD2 (which are involved in cortisone-cortisol interconversion). B. abortus infection did not modify 11β-HSD1 expression and GRα/β ratio in the presence or absence of adrenal steroids. Supernatants from B. abortus-infected monocytes induced 11β-HSD1 in synovial cells. Administration of cortisone was capable of inhibiting the secretion of RANKL by synoviocytes mimicking cortisol's effect. These results go along with previous observations that highlighted the ability of synovial tissue to secrete active steroids, making it an intracrine tissue. This is the first study that contributes to the knowledge of the consequence of adrenal steroids on synoviocytes in the context of a bacterial infection.
Highlights
Brucellosis is an infection caused by bacteria of the genus Brucella
We have demonstrated that Brucella infects and survives within human synoviocytes, and this infection elicits a proinflammatory microenvironment with the secretion of interleukin (IL)-6 and the chemokines IL-8; chemoattractant of neutrophils and monocyte chemoattractant protein 1 (MCP-1); chemoattractant of monocytes; and the secretion of matrix metalloproteases (MMPs) and RANKL—with concomitant osteoclastogenesis [7, 8]
During the administration of cortisol and DHEA in conjunction, no differences were observed in intracellular bacterial survival with respect to untreated cells, indicating that DHEA avoided the effect of cortisol These differences were significant at 24, 48, and 72 h postinfection (Figures 1A,B)
Summary
Brucellosis is an infection caused by bacteria of the genus Brucella. This is one of the infectious diseases transmissible between animals and humans. Brucella osteoarthritis is one of the most common features of human brucellosis. The most frequent joint involvements are spondylitis, arthritis, and osteomyelitis [1, 2]. The acute and the chronic forms of human brucellosis present joint involvement. In about 50% of the cases of osteoarciular brucellosis, bacteria are isolated from synovial fluid samples. The synovial membrane may present a lymphomononuclear infiltrate in the chronic phase of the disease, but usually this takes place in the acute setting [5, 6]
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