Glucocorticoid receptor antagonist RU 486 treatment reduces periodontitis in Fischer 344 rats

Recent studies have shown that psychological stress can influence cutaneous barrier function, suggesting that this form of stress could trigger or aggravate skin disease. In the present study, we demonstrate that transfer of hairless mice to a different cage delays barrier recovery rates. Pretreatment with a phenothiazine sedative, chlorpromazine, before transfer of animals restored the kinetics of barrier recovery toward normal, suggesting that psychological stress is the basis for this alteration in barrier homeostasis. To determine the mechanism linking psychological stress to altered barrier recovery, we first demonstrated that plasma corticosterone levels increase markedly after transfer of animals to new cages and that pretreatment with chlorpromazine blocks this increase. Second, we demonstrated that the systemic administration of corticosterone delays barrier recovery. Finally, we demonstrated that pretreatment with the glucocorticoid receptor antagonist RU-486 blocks the delay in barrier recovery produced by systemic corticosterone, change of cage, or immobilization. These results suggest that psychological stress stimulates increased production of glucocorticoids, which, in turn, adversely affects permeability barrier homeostasis.

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Effects of Adrenalectomy and of Mineralocorticoid Receptor/Glucocorticoid Receptor Ligands in Female Brown Norway and Fischer 344 Rats and F1 Hybrids

Journal of Neuroendocrinology ◽

10.1046/j.1365-2826.2002.00802.x ◽

2002 ◽

Vol 14 (7) ◽

pp. 574-579 ◽

Cited By ~ 3

Author(s):

N. Marissal-Arvy ◽

P. Mormède

Keyword(s):

Glucocorticoid Receptor ◽

Mineralocorticoid Receptor ◽

F1 Hybrids ◽

Brown Norway ◽

Fischer 344 Rats ◽

Receptor Ligands ◽

Fischer 344

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Endogenous glucocorticoids released during acute toxic liver injury enhance hepatic IL-10 synthesis and release

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.276.1.g199 ◽

1999 ◽

Vol 276 (1) ◽

pp. G199-G205 ◽

Cited By ~ 5

Author(s):

Mark G. Swain ◽

Caroline Appleyard ◽

John Wallace ◽

Howard Wong ◽

Tai Le

Keyword(s):

Liver Injury ◽

Inflammatory Response ◽

Glucocorticoid Receptor ◽

Receptor Antagonist ◽

Mrna Expression ◽

Elevated Serum ◽

Ru 486 ◽

Tnf Α ◽

Toxic Liver Injury ◽

Acute Toxic

Endogenous glucocorticoids are known to play a role in the regulation of the inflammatory response possibly by modulating pro- and anti-inflammatory cytokine expression. We examined endogenous glucocorticoid secretion, hepatic damage, tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) mRNA expression and release in rats treated with carbon tetrachloride (CCl4) after treatment with vehicle or a glucocorticoid receptor antagonist (RU-486). Rats treated with CCl4 demonstrated striking elevations of plasma corticosterone levels. Inhibition of endogenous glucocorticoid activity by pretreatment with the glucocorticoid receptor antagonist RU-486 resulted in augmented CCl4-mediated hepatotoxicity, as reflected by histology and serum transaminase levels, which were independent of alterations in serum TNF-α levels or hepatic mRNA expression. CCl4 treatment resulted in enhanced hepatic IL-10 mRNA expression and elevated serum IL-10 levels, which were markedly attenuated by glucocorticoid receptor blockade. In summary, significant endogenous glucocorticoid release occurs during acute toxic liver injury in the rat and suppresses the inflammatory response independent of effects on TNF-α but possibly by upregulating hepatic IL-10 production.

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