LEUKEMIA INHIBITORY FACTOR, INTERFERON-GAMMA AND DEXAMETHASONE REGULATE N-GLYCOSYLATION OF ALPHA-1-PROTEASE INHIBITOR IN HUMAN HEPATOMA-CELLS

Hepatocytes respond to inflammatory stimuli by changing the synthesis and N-glycosylation of acute phase plasma proteins (APP). So far, inte rleukin (IL) 6, transforming growth factor beta (TGFbeta), tumor necro sis factor a (TNF) and IL-1 have been found to control N-glycosylation patterns of APP. Cytokines either increased (type 1) or decreased (ty pe II) the ratio of bi-relative to more branched N-glycans on APP. In this study, we describe the effect of leukemia inhibitory factor (LIF) , interferon gamma (INFgamma) and dexamethasone ( dex) on production o f alpha1-protease inhibitor (PI) and alpha1-antichymotrypsin (ACT) and on glycosylation of PI in the human hepatoma cell line HepG2. Cytokin es and dex were used separately and in various combinations including also IL-6 and TGFbeta. Production of the antiproteases was quantitated by immunoelectrophoresis of the proteins accumulated in the culture m edium. Glycosylation pattern of PI was assessed by crossed immunoaffin ity electrophoresis (CIAE) with Concanavalin A (Con A) as a ligand. Th e production of ACT and PI was increased by LIF, decreased by INFgamma and unaffected by dex. LIF and INFgamma each like IL-6, decreased PI- Con A reactivity while dex like TGFbeta enhanced PI-Con A reactivity. Combination of dex with LIF yielded additive effects while combination of dex with either INFgamma, L-6 or TGFbeta acted synergistically on PI-Con A reactivity. Combinations of multiple cytokines and dex produc ed additive, inhibitory or synergistic effects. The type of glycosylat ion profile of PI secreted by HepG2 cells depended on the composition and amounts of interacting cytokines and dex.