INTERLEUKIN-1-BETA AND INTERLEUKIN-6 STIMULATE 2-METHYLAMINOISOBUTYRIC ACID UPTAKE IN HEPG2 CELLS

The metabolic response to inflammation involves an increased uptake of amino acids in the liver, It has been suggested that cytokines, such as interleukin-1 beta and interleukin-6, could be involved in this inc reased amino acid uptake, We investigated the role of these two inflam matory cytokines in regulating hepatic amino acid transport systems in the human hepatoma cell line, HepG2, Uptake of methylaminoisobutyric acid, the most specific known substrate of system A, and of glutamine, both transported by other sodium-dependent transport systems ASC and N, was assayed after incubation of the cells for various times with cy tokines, using the cluster-tray method, Interleukin-1 beta and interle ukin-6 (1000 U/ml) stimulated methylaminoisobutyric acid uptake by 36 +/- 6 and 41 +/- 4%, respectively (per cent +/- SD, n greater than or equal to 6), Under our experimental conditions, these cytokines had no effect on glutamine uptake, The stimulatory effect on methylaminoisob utyric acid uptake was not increased by combining the cytokines or by the presence of dexamethasone. The cytokine effect was abolished by cy cloheximide, suggesting the involvement of Je novo protein synthesis i n this activation of transport system A, These data demonstrate that, in our culture conditions, interleukin-6 and interleukin-6 indirectly exert a stimulatory effect on methylaminoisobutyric acid transport in HepG2 cells. (C) 1997 Elsevier Science Ltd.