Interleukin-1beta and interleukin-6 increase levels of apolipoprotein B mRNA and decrease accumulation of its protein in culture medium of HepG2 cells.

Abstract

The purpose of the present study was to examine the regulation of levels of apolipoprotein B (apoB) mRNA and its protein by cytokines in HepG2 cells. A dose-dependent increase in apoB mRNA levels was observed in the presence of either interleukin-1beta (IL-1beta) or IL-6 alone. This increase occurred as early as 1 h after IL-1beta or IL-6 stimulation. Exogenous addition of IL-1beta (5 ng/ml) and IL-6 (50 ng/ml) induced 2.8- and 2.1-fold increases as a result of 18 h of culture, respectively. Co-stimulation with IL-1beta and IL-6 significantly enhanced the increase in apoB mRNA levels stimulated with either cytokine alone. Treatment with cycloheximide prevented the induction of apoB mRNA by IL-1beta, but not by IL-6. These findings suggest that enhancement of apoB mRNA levels by these cytokines is mediated through different pathways. Conversely, IL-1beta and IL-6 lowered the accumulation of apoB protein levels in the culture medium. The pulse-chase study showed that addition of N-acetyl leucyl leucyl norleucinal to the medium induced a decrease in newly synthesized apoB in the cell lysate in response to IL-1beta (P < 0.05) or IL-6 (not to a significant extent) compared with control. These findings demonstrated that the lower level of apoB in the medium was caused by the enhanced intracellular degradation. In addition, IL-1beta increased LDL receptor mRNA levels as well as protein activity, although IL-6 did not, suggesting that the more marked decrease in apoB accumulation in the medium induced by IL-1beta compared with that induced by IL-6 may reflect an increased uptake of apoB from the medium by IL-1beta. The present study demonstrates that a cytokine network may be involved in the metabolism of apoB under certain conditions such as inflammation.