Constitutive expression of IL-18 and IL-18R in differentiated IEC-6 Constitutive expression of IL-18 and IL-18R in differentiated IEC-6 cells: Effect of TNF- α and IFN- γ treatment cells: Effect of TNF-and IFN-treatment

The multifunctional cytokine interleukin-18 (IL-18) is an important mediator in intestinal inflammatory processes. The aim of this study was to evaluate the constitutive expression of IL-18 and its receptors (IL-18R (cid:2) and IL-18R (cid:3) ) in intestinal epithelial cells (IEC) stimulated by tumor necrosis factor- (cid:2) (TNF- (cid:2) ) and interferon- (cid:4) (IFN- (cid:4) ). In addition, cellular proliferation and evaluation of brush border enzymes as differentiation markers were studied. Nontransformed rat intestinal epithelial IEC-6 cells were grown on an extracellular matrix (ECM) in medium with or without TNF- (cid:2) , IFN- (cid:4) , or a combination of both. Gene expression of IL-18, its receptors and apoptotic markers was evaluated using real-time PCR. Expression of IL-18R (cid:2) protein was demonstrated by flow cytometry and Western blot. Enzymatic activities of brush border enzymes and caspase-1 were determined. The constitutive expression of IL-18, IL-18R (cid:2) and IL-18R (cid:3) mRNAs and proteins were detected in IEC-6 cells. The biologically active form of IL-18 was released in response to TNF- (cid:2) and IFN- (cid:4) treatment. Exogenous IL-18 had no effect on cellular proliferation, brush border enzyme activities, and gene expression of apoptotic markers. However, the addition of IL-18 stimulated production and release of the chemokine IL-8. These data suggest that IEC-6 cells may be not only a source of IL-18 but also a target for its action. IL-18R the producing differentiated cells and cells were used to eluci-date the mechanisms of on differentiated cells.