Gentilini María Virginia, Giambartolomei Guillermo Hernán, Delpino María Victoria
Instituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Front Endocrinol (Lausanne). 2019 Oct 22;10:722. doi: 10.3389/fendo.2019.00722. eCollection 2019.
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 infection of synoviocytes creates a proinflammatory microenvironment. We proposed to determine the role of cortisol and DHEA on synoviocytes and infiltrating monocytes during infection. Cortisol inhibited IL-6, IL-8, MCP-1, and MMP-2 secretion induced by infection in synovial fibroblast. Cortisol-mediated MMP-2 inhibition during infection was reversed by IL-6. DHEA inhibited induced RANKL up-regulation in synovial fibroblast through estrogen receptor (ER). 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). infection did not modify 11β-HSD1 expression and GRα/β ratio in the presence or absence of adrenal steroids. Supernatants from -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.
刺激炎症免疫反应，进而刺激内分泌系统，诱导脱氢表雄酮（DHEA）和皮质醇的分泌。在人类中，活动性疾病通常表现为骨关节布鲁氏菌病。在先前的研究中，我们表明滑膜细胞感染会产生促炎微环境。我们提议确定皮质醇和DHEA在感染期间对滑膜细胞和浸润单核细胞的作用。皮质醇抑制滑膜成纤维细胞感染诱导的白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、单核细胞趋化蛋白-1（MCP-1）和基质金属蛋白酶-2（MMP-2）的分泌。感染期间皮质醇介导的MMP-2抑制作用被IL-6逆转。DHEA通过雌激素受体（ER）抑制滑膜成纤维细胞中诱导性核因子κB受体活化因子配体（RANKL）的上调。感染并未调节糖皮质激素受体（GR）的表达。根据11β-羟基类固醇脱氢酶（HSD）1型和11β-HSD2型同工酶的活性（它们参与可的松-皮质醇的相互转化），细胞对皮质醇的反应还取决于其细胞内生物利用度。无论有无肾上腺类固醇，感染均未改变11β-HSD1的表达和GRα/β比值。感染单核细胞的上清液可诱导滑膜细胞中的11β-HSD1。给予可的松能够抑制滑膜细胞分泌RANKL，模拟皮质醇的作用。这些结果与先前的观察结果一致，即突出了滑膜组织分泌活性类固醇的能力，使其成为一个自分泌组织。这是第一项有助于了解细菌感染情况下肾上腺类固醇对滑膜细胞影响的研究。
