In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 300, No. 6 ( 2011-06), p. C1306-C1313
Abstract:
Ca + -dependent signaling regulates the function of dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity. The activity of DCs is suppressed by glucocorticoids, potent immunosuppressive hormones. The present study explored whether the glucocorticoid dexamethasone influences the cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in DCs. To this end, DCs were isolated from mouse bone marrow. According to fura-2 fluorescence, exposure of DCs to lipopolysaccharide (LPS, 100 ng/ml) increased [Ca 2+ ] i , an effect significantly blunted by overnight incubation with 10 nM dexamethasone before LPS treatment. Dexamethasone did not affect the Ca 2+ content of intracellular stores, sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA)2 and SERCA3 expression, ryanodine receptor (RyR)1 expression, or Ca 2+ entry through store-operated Ca 2+ channels. In contrast, dexamethasone increased the transcript level and the membrane protein abundance of the Na + /Ca 2+ exchanger NCX3. The activity of Na + /Ca 2+ exchangers was assessed by removal of extracellular Na + in the presence of external Ca 2+ , a maneuver triggering the Ca 2+ influx mode. Indeed, Na + removal resulted in a rapid transient increase of [Ca 2+ ] i and induced an outwardly directed current as measured in whole cell patch-clamp experiments. Dexamethasone significantly augmented the increase of [Ca 2+ ] i and the outward current following removal of extracellular Na + . The NCX blocker KB-R7943 reversed the inhibitory effect of dexamethasone on LPS-induced increase in [Ca 2+ ] i . Dexamethasone blunted LPS-induced stimulation of CD86 expression and TNF-α production, an effect significantly less pronounced in the presence of NCX blocker KB-R7943. In conclusion, our results show that glucocorticoid treatment blunts LPS-induced increase in [Ca 2+ ] i in DCs by increasing expression and activity of Na + /Ca 2+ exchanger NCX3. The effect contributes to the inhibitory effect of the glucocorticoid on DC maturation.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00396.2010
Language:
English
Publisher:
American Physiological Society
Publication Date:
2011
detail.hit.zdb_id:
1477334-X
SSG:
12
