The proinflammatory cytokine, interleukin-1alpha, reduces glucocorticoid receptor translocation and function.

Abstract:

:Proinflammatory cytokines have been shown to influence the expression and function of the glucocorticoid receptor (GR). Specifically, several studies have found that cytokines induce a decrease in GR function, as evidenced by reduced sensitivity to glucocorticoid effects on functional end points. To investigate the potential mechanism(s) involved, we examined the impact of the proinflammatory cytokine, interleukin-1alpha (IL-1alpha), on 1) GR translocation from cytoplasm to nucleus using GR immunostaining, 2) cytosolic radioligand GR binding, and 3) GR-mediated gene transcription in L929 cells stably transfected with the mouse mammary tumor virus-cholamphenicol acetyltransferase reporter gene. L929 cells were treated with IL-1alpha (100 and 1000 U/ml) for 24 h in the presence or absence of dexamethasone (Dex; 10 nM to 1 microM). IL-1alpha inhibited Dex-induced GR translocation and alone induced GR up-regulation. Pretreatment with IL-1alpha followed by Dex treatment for 1.5 h led to about 20% inhibition of Dex-induced GR-mediated gene transcription, whereas coincubation of IL-1alpha plus Dex for 24 h inhibited Dex-induced GR-mediated gene activity up to 42%. The latter effect was reversed by the IL-1 receptor antagonist. These results suggest that cytokines produced during an inflammatory response may induce GR resistance in relevant cell types by direct effects on the GR, thereby providing an additional pathway by which the immune system can influence the hypothalamic-pituitary-adrenal axis.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Pariante CM,Pearce BD,Pisell TL,Sanchez CI,Po C,Su C,Miller AH

doi

10.1210/endo.140.9.6986

subject

Has Abstract

pub_date

1999-09-01 00:00:00

pages

4359-66

issue

9

eissn

0013-7227

issn

1945-7170

journal_volume

140

pub_type

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