Premium
Glucocorticoids exert opposing effects on macrophage function dependent on their concentration
Author(s) -
Lim HeeYoung,
Müller Nora,
Herold Marco J.,
Van Den Brandt Jens,
Reichardt Holger M.
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02611.x
Subject(s) - corticosterone , glucocorticoid , mineralocorticoid , immune system , glucocorticoid receptor , biology , endocrinology , macrophage , medicine , in vivo , chemokine , steroid hormone , adrenalectomy , hormone , receptor , mineralocorticoid receptor , aldosterone , microbiology and biotechnology , in vitro , immunology , biochemistry
Summary Glucocorticoids (GCs) are involved in the modulation of macrophage function and thereby control the host's immune responses to pathogens. However, neither the role of hormone concentration nor the differential contribution of the glucocorticoid (GR) and the mineralocorticoid receptors (MR) to these activities are known. Here we show that low levels of corticosterone enhance NO production as well as mRNA expression of pro‐inflammatory cytokines, chemokines and enzymes required for mediator synthesis. In contrast, at high corticosterone concentrations macrophage function was strongly repressed. Importantly, inactivation of the GR by lentiviral delivery of siRNAs abrogated both the immunostimulatory and the immunosuppressive GC actions whereas inactivation of the MR had no effect. Furthermore, removal of endogenous GCs by adrenalectomy in vivo induced a preactivated state in macrophages that could be modulated by corticosterone. We conclude that GCs exert distinct effects on macrophage function dependent on their concentration, and that they primarily act through the GR despite concomitant expression of the MR.