Dexamethasone inhibits IFNγ-induced MHC class II expression of intestinal epithelial cells independently of the TGF-β1 regulatory pathway

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Abstract

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.

Aim:

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-β1 regulatory pathway in mediating the effects of dexamethasone, neutralizing anti-TGF-β antibodies were used. Additionally, endogenous and dexamethasone-stimulated IEC-6 cell TGF-β1 production was measured by ELISA.

Results:

Dexamethasone potently down-regulated IFNγ-induced class II expression on IEC-6 cells, in a dose-dependent manner. TGF-β1 had a similar inhibitory effect on class II expression. However, neutralizing anti-TGF-β antibodies did not alter the effect of dexamethasone. Furthermore, dexamethasone reduced endogenous TGF-β1 synthesis.

Conclusions:

Corticosteroids inhibit cytokine-induced MHC class II expression on IEC-6 cells in a TGF-β1 independent way. This effect may markedly alter enterocytic antigen presentation, reducing the aberrant state of activation of mucosal immune cells.

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