SUPPRESSIVE EFFECT OF ETHANOL ON THE EXPRESSION OF HEPATIC ASIALOGLYCOPROTEIN RECEPTORS AUGMENTED BY INTERLEUKIN-1-BETA, INTERLEUKIN-6, ANDTUMOR-NECROSIS-FACTOR-ALPHA

Blood levels of inflammatory-related cytokines, including interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha, are elevated in patients with alcoholic liver diseases. We investigated the effect s of these cytokines and ethanol on the expression of hepatic asialogl ycoprotein receptors (AGPRs) in a human hepatoblastoma cell line, HepG 2. An [I-125]-asialo-orosomucoid binding assay showed significant incr eases in surface AGPR numbers in HepG2 cells by treatment with IL-1 be ta, IL-6, and TNF-alpha, to levels which were approximately 130% of th e values in untreated control cells. However, the enhanced AGPR number s induced by treatment with these cytokines were markedly suppressed, to 70%-80% of the number in the untreated cells, by treatment with eth anol. Immunological detection of AGPR with a specific antibody demonst rated that the modulation of surface AGPR numbers was correlated with the cellular expression levels of AGPR. These results suggest that, al though IL-1 beta, IL-6, and TNF-alpha stimulate the synthesis of hepat ic AGPR, ethanol suppresses the expression of AGPR augmented by these cytokines. This leads to an increase in serum asialo-orosomucoid level s caused by the disordered catabolism mediated by AGPR in patients wit h alcoholic liver diseasde.