Analysis of glucocorticoid receptors and their apoptotic response to dexamethasone in male murine B cells during development.

Glucocorticoids have an important role in the resolution of inflammation and clinically they are routinely used to treat allergies, asthma, sepsis, and autoimmune diseases. In addition, glucocorticoids are well recognized to negatively impact the development and function of T cells in the immune system by inducing apoptosis. Less is known however about glucocorticoid function in B lymphocytes. Herein, we demonstrate that the glucocorticoid receptor (GR) is present in B-cell populations isolated from both the spleen and the bone marrow. B-cell populations were found to express more GR than non-B-cell populations from both the spleen and the bone marrow. GR protein was found in all B-cell (B220+) developmental subsets (Mature IgM+IgD+, Immature IgM+IgD-, and Pro/Pre IgM-IgD-) isolated from spleen. GR staining intensity was varied among the B-cell developmental subsets and was found to be higher in B cells isolated from the spleen (secondary lymphoid organ) versus the bone marrow (primary lymphoid organ). Ex vivo cell culture of murine splenocytes and bone marrow lymphocytes indicated that dexamethasone stimulated apoptosis in all B-cell developmental subsets demonstrating glucocorticoid responsiveness. Furthermore, in vivo administration of dexamethasone to adrenalectomized mice reduced B-cell numbers in both spleen and bone marrow. These data suggest that glucocorticoid signaling has an important understudied role in B-cell life-or-death decisions.

Tissue-specific actions of glucocorticoids on apoptosis: a double-edged sword.

First described for their metabolic and immunosuppressive effects, glucocorticoids are widely prescribed in clinical settings of inflammation. However, glucocorticoids are also potent inducers of apoptosis in many cell types and tissues. This review will focus on the established mechanisms of glucocorticoid-induced apoptosis and outline what is known about the apoptotic response in cells and tissues of the body after exposure to glucocorticoids. Glucocorticoid-induced apoptosis affects the skeletal system, muscular system, circulatory system, nervous system, endocrine system, reproductive system, and the immune system. Interestingly, several cell types have an anti-apoptotic response to glucocorticoids that is cytoprotective. Lastly, we will discuss the pro- and anti-apoptotic effects of glucocorticoids in cancers and their clinical implications.