Fm. Ruemmele et al., Dexamethasone inhibits IFN gamma-induced MHC class II expression of intestinal epithelial cells independently of the TGF-beta 1 regulatory pathway, ALIM PHARM, 13(5), 1999, pp. 595-601
Background: In the presence of inflammation, an increased expression of ent
erocyte MHC class II is observed, leading to altered mucosal antigen handli
ng, Corticosteroids are potent anti-inflammatory drugs, widely used in trea
ting inflammatory bowel disorders, However, their diverse mechanisms of act
ion are only partially understood,
Aim: To evaluate effect and mechanisms of corticosteroids on intestinal cry
pt epithelial cell MHC class II.
Methods: The effect of dexamethasone treatment on cytokine-induced MHC clas
s II expression was measured in IEC-6 cells by immunofluorescence and flow
cytometry. To determine the role of the TGF-beta 1 pathway in mediating the
effects of cytometry. regulatory dexamethasone, neutralizing anti-TGF-beta
antibodies were used. Additionally, endogenous and dexamethasone-stimulate
d IEC-6 cell TGF-beta 1 production was measured by ELISA.
Results: Dexamethasone potently down-regulated IFN gamma-induced class II e
xpression on IEC-6 cells, in a dose-dependent manner, TGF-beta 1 had a simi
lar inhibitory effect on class II expression, However, neutralizing anti-TG
F-beta antibodies did not alter the effect of dexamethasone, Furthermore, d
examethasone reduced endogenous TGF-beta 1 synthesis.
Conclusions: Corticosteroids inhibit cytokine-induced MHC class II expressi
on on IEC-6 cells in a TGF-beta 1 independent way. This effect may markedly
alter enterocytic antigen presentation, reducing the aberrant state of act
ivation of mucosal immune cells.