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Published on: December 26, 2017
Glucocorticoids exert opposing effects on macrophage function dependent on their concentration.
Hee-Young Lim1, Nora Müller, Marco J Herold
1Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Glucocorticoids (GCs) modulate macrophage immune responses. Low hormone levels enhance, while high levels repress, macrophage function, primarily through the glucocorticoid receptor (GR).
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Glucocorticoids (GCs) are critical regulators of macrophage function and immune responses.
- The influence of hormone concentration and the specific roles of glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) in mediating these effects remain unclear.
Purpose of the Study:
- To investigate the concentration-dependent effects of corticosterone on macrophage function.
- To determine the distinct roles of the GR and MR in mediating glucocorticoid actions on macrophages.
Main Methods:
- Macrophages were treated with varying concentrations of corticosterone.
- Glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) functions were inactivated using lentiviral siRNA delivery.
- Macrophage function was assessed by measuring nitric oxide (NO) production and pro-inflammatory gene expression.
- Adrenalectomy was performed in vivo to remove endogenous GCs, followed by corticosterone modulation.
Main Results:
- Low corticosterone concentrations enhanced NO production and pro-inflammatory gene expression in macrophages.
- High corticosterone concentrations led to significant repression of macrophage function.
- Inactivation of the GR abolished both stimulatory and suppressive GC effects, while MR inactivation had no impact.
- Adrenalectomy induced a preactivated macrophage state, sensitive to corticosterone modulation.
Conclusions:
- Glucocorticoids exert distinct, concentration-dependent effects on macrophage function.
- These effects are primarily mediated through the glucocorticoid receptor (GR), irrespective of mineralocorticoid receptor (MR) presence.
- Understanding these mechanisms is crucial for modulating immune responses in various physiological and pathological conditions.
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