Control of apolipoprotein E secretion in the human hepatoma cell line KYN-2

Even though it is known that apolipoprotein E (apoE) is deeply involved in major age-related disorders such as atherosclerosis or Alzheimer's disease (AD), the control of cell-specific apoE expression is still poorly understo od. We compared the apoE secretion as previously described in astrocytic ce lls to hepatic cell apoE secretion. We used the human hepatoma cell line KY N-2 to better delineate the characteristics of apoE secretion and to valida te it with respect to the classical human hepatoma cell line HepG2. Interle ukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) significantly inhi bited, while IL-2, IL-6 and tumour necrosis factor-alpha (TNF-alpha) were i nactive on apoE secretion by KYN-2 as well as HepG2 cells. Cholesterol and 25-OH cholesterol had no effect, while forskolin exerted a significant inhi bitory effect, on apoE secretion in KYN-2 cells. Our results suggest that t he KYN-2 cell line represents an appropriate cell model, and in any case an alternative model to the HepG2 cell line, to study the control of apoE sec retion. The response of KYN-2 cells to both cytokines and cholesterol diffe rs from that found in astrocytoma cells, suggesting that blood variations o f apoE concentrations in AD may not reflect the dysregulations taking place in the brain. Copyright (C) 2001 John Wiley Be Sons, Ltd.