TUMOR-NECROSIS-FACTOR-ALPHA AUGMENTS THE EXPRESSION OF GLUCOSE-6-PHOSPHATE-DEHYDROGENASE IN RAT HEPATIC ENDOTHELIAL AND KUPFFER CELLS

Cellular activity of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose monophosphate shunt, supports several pathways i nvolved in the nonspecific immune response. In the present study, we i nvestigated the in vivo effects of selected pro-inflammatory cytokines on the expression of G6PD in Kupffer and hepatic endothelial cells. M urine recombinant TNF alpha, IL-1 beta, or IL-6 (1.5x10(5) U/kg) was i njected and cellular G6PD mRNA level determined using a quantitative r everse transcription and polymerase chain reaction method. G6PD mRNA w as elevated two- to threefold seven hours after the injection of TNF a lpha in Kupffer and endothelial cells as compared to cells from saline -injected animals. The elevated G6PD mRNA was accompanied by increased cellular enzyme activity in both cells. The cellular activity of 6-ph osphogluconate dehydrogenase (6PGD) was also increased seven hours aft er TNF alpha treatment in these cells. G6PD mRNA and enzyme activity r eturned to control levels 22h after TNF alpha administration. In contr ast to the marked effects of TNF alpha, no significant alterations wer e found on G6PD expression following IL-1 beta or IL-6 injections in t hese cells. None of these cytokines caused changes in G6PD or 6PGD exp ression in parenchymal cells. These data indicate that the proinflamma tory cytokine TNF alpha plays an important role in the regulation of c ellular G6PD expression in hepatic immune competent cells.