Article Text

Download PDFPDF
Glucocorticoid receptors are downregulated in hepatic T lymphocytes in rats with experimental cholangitis
  1. K Tjandra,
  2. T Le,
  3. M G Swain
  1. Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada T2N 1N4
  1. Correspondence to:
    Dr M G Swain, Gastrointestinal Research Group, Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 1N4;


Background and aims: Primary sclerosing cholangitis is a Th1 cytokine driven disease with a poor clinical responsiveness to glucocorticoid therapy. We have previously documented elevated circulating glucocorticoid levels in cholestatic rats and in addition have noted increased hepatic expression of the Th1 cytokine interferon γ (IFN-γ) in a rat model of cholangitis. Therefore, we examined the relationship between circulating glucocorticoid levels, hepatic IFN-γ expression, and hepatic T cell glucocorticoid receptor (GR) expression in a rat model of cholangitis to provide insight into the possible mechanism underlying hepatic T cell glucocorticoid resistance in cholangitic diseases.

Methods: Cholangitis was induced in male Sprague-Dawley rats by oral administration of low dose α-naphthylisothiocyanate (ANIT). On day 14, ANIT fed and control rats were sacrificed, serum collected, and hepatic, splenic, and peripheral blood T lymphocytes isolated for GR expression, as determined by reverse transcription-polymerase chain reaction and western blotting.

Results: Circulating glucocorticoid levels were markedly elevated in ANIT fed rats. Hepatic T lymphocyte GR mRNA and protein levels were significantly reduced in ANIT treated rats compared with controls. In contrast, GR mRNA and protein expression in splenic and circulating T lymphocytes was similar in both groups. Furthermore, reduced hepatic T cell GR expression in ANIT fed rats was associated with reduced hepatic CD4+ T cell sensitivity to dexamethasone inhibitory effects (that is, inhibition of interleukin 2 receptor expression).

Conclusion: We conclude that hepatic T lymphocyte resistance to elevated endogenous glucocorticoid levels in rats with experimental cholangitis appears, in part, to be mediated by decreased GR expression.

  • hepatic cytokines
  • primary sclerosing cholangitis
  • glucocorticoid sensitivity
  • PSC, primary sclerosing cholangitis
  • IL, interleukin
  • IL-2R, IL-2 receptor
  • IFN, interferon
  • DHEA, dehydroepiandrosterone
  • IBD, inflammatory bowel disease
  • GR, glucocorticoid receptor
  • PBC, primary biliary cirrhosis
  • ANIT, α-naphthylisothiocyanate
  • PBS, phosphate buffered saline
  • FITC, fluorescein isothiocyanate
  • PE, phycoerythrin
  • RT-PCR, reverse transcription-polymerase chain reaction
  • TNF, tumour necrosis factor
  • FACS, fluorescence activated cell sorter
  • ConA, concanavalin A
  • NK, natural killer
  • GAPDH, glyceraldehyde-3-phosphate dehydrogenase
  • PBMC, peripheral blood mononuclear cells

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.