High levels of glucocorticoid receptors in patients with active Crohn's disease may predict steroid resistance

R. Towers, Timna Naftali, G. Gabay, M. Carlebach, A. Klein, B. Novis

Research output: Contribution to journalArticlepeer-review

Abstract

Up to 20% of Crohn's disease (CD) patients respond poorly to glucocorticoids (GC). A product of an alternative splicing of the glucocorticoid receptor (GR) premRNA, GRβ, may play a role as a dominant inhibitor of the glucocorticoid response. Increasing evidence suggests that inflammatory cytokines such as interleukin (IL)-18 alternate the splicing of the primary transcript between the two isoforms GRβ and GRa in hGR gene of CD patients. The aim of this study is to assess the expression of GRα and GRβ in patients with CD and to look for a possible correlation between these receptors and the response to glucocorticoid treatment. Forty-two CD patients and 17 healthy volunteers were studied. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed using real-time PCR techniques. Serum IL-18 protein levels were measured by enzyme-linked immunosorbent assay (ELISA). The amount of hGRα-mRNA in patients in remission was significantly lower than in controls (P < 0.05). The amount of hGRβ-mRNA was significantly higher in GC-resistant patients in the active stage of disease compared with all other groups (P < 0.05). Patients in the active stage of the disease had higher levels of IL-18 than patients in remission and both had higher levels than controls (P < 0.05). The amounts of IL-18 were directly correlated with the amount of hGRβ mRNA in GC-resistant patients with an active disease. High levels of hGRβ might be connected to GC resistance. IL-18 might participate in the alternative splicing of the hGR preliminary mRNA of CD patients. The results support the theory that augmented hGRβ mRNA expression level in PBMC is connected with GC-resistance of CD patients.

Original languageEnglish
Pages (from-to)357-362
Number of pages6
JournalClinical and Experimental Immunology
Volume141
Issue number2
DOIs
StatePublished - Aug 2005

Keywords

  • Crohn's disease
  • Glucocorticoid receptor alpha
  • Glucocorticoid receptor beta
  • Glucocorticoid receptor mRNA
  • IL-18

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