Recombinant interleukin 6 regulates the transcriptional activation of a set of human acute phase genes

The phenomenon of acute phase (AP) response can be reproduced in vitro using cultured cells of hepatic origin by stimulation with the crude supernatant of activated monocytes (MoCM). Several monocyte-derived factors have been identified which might be responsible, alone or in combination, for the induction of AP response, but recently the attention has been focused on interleukin 6 (IL-6). We have previously shown that part of the AP response consists of the increase in the rate of transcription of the AP genes. Here we have treated the human hepatoma cell line Hep 3B with either crude MoCM or recombinant IL-6 and compared the effect of the two stimulants on the expression of both endogenous AP genes and recombinant plasmids introduced into the cells by transfection. The transfected plasmids contained the 5'-flanking region of AP genes fused to the coding region of the bacterial chloramphenicol acetyltransferase gene. We observe that the induction of mRNA accumulation of the endogenous genes corresponds to the transcriptional activation of the chloramphenicol acetyltransferase fusions. This is good evidence that the effect of IL-6 is totally or partially exerted at the level of transcription and that short segments of the 5'-flanking sequences of the inducible genes contain IL-6-responsive elements. Our results show that IL-6 is fully effective only on some of all the genes induced or repressed by MoCM, whereas others are only partially affected or totally nonresponsive.