Unknown

Dataset Information

0

Resistance of LPS-activated bone marrow derived macrophages to apoptosis mediated by dexamethasone.


ABSTRACT: Glucocorticoids (GC) display pleiotropic effects on the immune system. Macrophages are a major target for GC action. Here we show that dexamethasone (DEX), a synthetic GC, decreased viability of naïve bone marrow-derived macrophages (BMDM), involving an apoptotic mechanism. Administration of DEX together with lipopolysaccharide (LPS) protected BMDM against DEX-mediated cell death, suggesting that activated BMDM respond to DEX differently than naïve BMDM. An insight to the molecular basis of LPS actions was provided by a 7 fold increase in mRNA levels of glucocorticoid receptor beta (GRβ), a GR dominant-negative splice variant which inhibits GRα's transcriptional activity. LPS did not inhibit all DEX-mediated effects on BMDM; DEX significantly reduced the percentage of BMDM expressing high levels of the cell surface markers F4/80 and CD11b and led to a decrease in macrophage inflammatory protein 1 alpha (MIP1-α) mRNA and protein levels. These two DEX-mediated effects were not prevented by LPS. Our finding that LPS did not reduce the DEX-induced elevation of glucocorticoid-induced leucine zipper (GILZ), a mediator of GCs anti-inflammatory actions, may provide an underlying mechanism. These findings enable a better understanding of clinical states, such as sepsis, in which macrophages are activated by endotoxins and treatment by GCs is considered.

SUBMITTER: Haim YO 

PROVIDER: S-EPMC3948355 | biostudies-other | 2014

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC4652239 | biostudies-literature
| S-EPMC1221572 | biostudies-other
| S-EPMC5526519 | biostudies-literature
| S-EPMC5647029 | biostudies-literature
| S-EPMC8581492 | biostudies-literature
| S-EPMC10060350 | biostudies-literature
2022-05-05 | GSE160246 | GEO
2024-01-26 | PXD041375 | Pride
| S-EPMC7005081 | biostudies-literature
2023-08-09 | GSE213051 | GEO