Regulatory effects of multifunctional cytokines and steroid hormones on apolipoprotein B production by human fetal hepatocytes.
OBJECTIVE
The purpose of the present investigation was to determine the effects of certain multifunctional cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], 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-alpha, IL-1 beta, 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 (10(6) 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-alpha maximally inhibited Apo B production by 50% at a half-maximal concentration of 100 pg/mL, whereas IL-1 beta 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-alpha, IL-1 beta, or IL-6 did not significantly affect hepatocyte viability. At physiologic concentrations (1 mumol/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.


CONCLUSIONS
Tumor necrosis factor-alpha and IL-1 beta 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.
Kutteh
W H
WH
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9032, USA.
Rainey
W E
WE
Carr
B R
BR
D001055:Apolipoproteins B / Q000096:biosynthesis*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007728:Kupffer Cells; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D019899:Paracrine Communication; D013256:Steroids / Q000494:pharmacology*
D001055:Apolipoproteins B; D016207:Cytokines; D013256:Steroids