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Regulatory Effects of Multifunctional Cytokines and Steroid Hormones on Apolipoprotein B Production by Human Fetal Hepatocytes

William E. Rainey

Bruce R. Carr

OBJECTIVE: The purpose of the present investigation was to determine the effects of certain multifunctional cytokines (tumor necrosis factor- [TNF-], interleukin-1ß [IL-1ß], and IL-6) and steroid hormones (estradiol, testosterone, progesterone, and cortisol) on the production of apolipoprotein B (Apo B) by cultured human fetal hepatocytes. We conducted these experiments because of our recent observations that purified human fetal Kupffer cells produce TNF-, IL-1ß, and IL-6.

METHODS: Human fetal hepatocytes, specifically depleted of hematopoietic precursors and Kupffer cells, were cultured in defined medium. The amounts of Apo B released into the culture medium were measured by a sensitive and specific enzyme-linked immunosorbent assay.

RESULTS: Hepatocytes (106 cells) produced 82 ± 16 ng Apo B per 24 hours during days 4-7 in culture. Results demonstrated that treatment of cultured hepatocytes with TNF- maximally inhibited Apo B production by 50% at a half-maximal concentration of 100 pg/mL, whereas IL-1ß maximally inhibited Apo B production by 80% at a half-maximal dose of 200 pg/mL. Cells exposed to IL-6 produced increased amounts of Apo B, but only after IL-6 was removed from the culture medium. The addition of TNF-, IL-1ß, or IL-6 did not significantly affect hepa tocyte viability. At physiologic concentrations (1 µmol/L), estrogens were able to increase the production of Apo B by 25-65%; however, no positive or negative effect could be demonstrated with dexamethasone, cortisol, testosterone, or progesterone. When using synthetic estrogens such as ethinyl estradiol and mestranol, the stimulatory effect was most pronounced.

CONCLUSION: Tumor necrosis factor- and IL-1ß have an inhibitory effect and estrogens have a stimulatory effect on Apo B production by human fetal hepatocytes in culture. These studies suggest that fetal hepatocytes can produce Apo B and that the synthesis of Apo B is under the control of multifunctional cytokines and steroid hormones. (J Soc Gynecol Invest 1994 ;1 :256-63)

Key Words: Fetal Kupffer cells • fetal hepatocytes • cytokines • interleukins • apolipoprotein B.

Journal of the Society for Gynecologic Investigation, Vol. 1, No. 4, 256-263 (1994)
DOI: 10.1177/107155769400100403


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