Dexamethasone inhibits IFNgamma-induced MHC class II expression of intestinal epithelial cells independently of the TGF-beta1 regulatory pathway.
BACKGROUND
In the presence of inflammation, an increased expression of enterocyte MHC class II is observed, leading to altered mucosal antigen handling. Corticosteroids are potent anti-inflammatory drugs, widely used in treating inflammatory bowel disorders. However, their diverse mechanisms of action are only partially understood.


OBJECTIVE
To evaluate effect and mechanisms of corticosteroids on intestinal crypt epithelial cell MHC class II.


METHODS
The effect of dexamethasone treatment on cytokine-induced MHC class II expression was measured in IEC-6 cells by immunofluorescence and flow cytometry. To determine the role of the TGF-beta1 regulatory pathway in mediating the effects of dexamethasone, neutralizing anti-TGF-beta antibodies were used. Additionally, endogenous and dexamethasone-stimulated IEC-6 cell TGF-beta1 production was measured by ELISA.


RESULTS
Dexamethasone potently down-regulated IFNgamma-induced class II expression on IEC-6 cells, in a dose-dependent manner. TGF-beta1 had a similar inhibitory effect on class II expression. However, neutralizing anti-TGF-beta antibodies did not alter the effect of dexamethasone. Furthermore, dexamethasone reduced endogenous TGF-beta1 synthesis.


CONCLUSIONS
Corticosteroids inhibit cytokine-induced MHC class II expression on IEC-6 cells in a TGF-beta1 independent way. This effect may markedly alter enterocytic antigen presentation, reducing the aberrant state of activation of mucosal immune cells.
Ruemmele
F M
FM
Intestinal Immunology Laboratory, Ste. Justine Hospital, Departments of Paediatrics and Nutrition, University of Montreal, Quebec, Canada.
Dionne
S
S
Levy
E
E
Seidman
E G
EG
D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007371:Interferon-gamma / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology*
D000949:Histocompatibility Antigens Class II; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D007371:Interferon-gamma