Glucocorticoid modulation of Ca²⁺ homeostasis in human B lymphoblasts

Abstract

Stimulation of B lymphocytes leads to diverse cellular functions including secretion, proliferation, differentiation or programmed cell death (apoptosis). Inflammatory agents binding or cross-linking surface membrane receptors increase protein kinaseÏphosphatase activities and activate phospholipase C, generating inositol 1,4,5-trisphosphate (IP×). IP× mobilizes Ca¥ from intracellular Ca¥ stores and produces a transient rise in cytosolic Ca¥ (Cafl). The emptying of Ca¥ from IP×-sensitive Ca¥ stores also results in enhanced Ca¥ influx across the plasma membrane, which is manifested as an enhancement of the Cafl transient, oscillatory increases in Cafl, or a secondary, sustained increase in [Ca¥]é. This Ca¥ entry pathway, termed storeoperated Ca¥ entry (SOCE), is responsible for refilling intracellular Ca¥ stores (Putney, 1990) and is an important regulator of Ca¥-dependent gene expression (Negulescu et al. 1994;Dolmetsch et al. 1998; for review, see Putney & Bird, 1993). In B lymphocytes, elevation of [Ca¥]é serves as a differentiation signal towards antibody-secreting cells (Clevers et al. 1985;Huang et al. 1995) and enables

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A2-dependent mechanism

“…This interpretation was supported by the results from experiments in which the effects of glucocorticoids on calcium uptake and concentrations were blocked by actinomycin D in the present and other studies (48). Results in other reports as well suggest that glucocorticoids regulate cellular calcium homeostasis through the classic GRmediated genomic mechanism rather than through rapid, nongenomic mechanisms (19,38,48).…”

“…In addition to muscle cells, the influence of glucocorticoids on calcium homeostasis has also been examined in other cell types, including thymocytes, mouse lymphoma cells, astrocytes, and human B lymphoblasts (6,19,38,48,66). In most of those studies, glucocorticoids increased calcium influx and cytosolic concentrations, and results were consistent with glucocorticoid-mediated changes in calcium stores and increased SOCE.…”

Glucocorticoid stimulation increases cardiac contractility by SGK1-dependent SOCE-activation in rat cardiac myocytes

“…Beside data that conditional GC-receptor overexpression may increase SR Ca load in isolated myocytes [22], there is few evidence in myocytes. In non-excitable cultured lymphoblastoid cell lines, however, cortisol incubation (200 nM, 48 h) has been shown to increase SR Ca content [23]. We show here that Dex exposure increased SR content measured by caffeine-induced transients in isolated cardiomyocytes (Fig 2D), which may at least partly explain the Dex-dependent stimulation of inotropy.…”

Corticosterone exerts immunostimulatory effects on macrophages via endoplasmic reticulum stress

“…ER stress is one of central mechanisms for maintenance of cellular homoeostasis, such as calcium homoeostasis and induction of apoptosis of injured cells. Glucocorticoids have been demonstrated to induce intracellular calcium changes and apoptosis in immune cells50, 51. Further studies are needed to investigate the part played by the ER stress response in modulating glucocorticoid‐induced calcium metabolism and apoptosis in macrophages.…”