Stimulation of angiotensinogen production in primary cultures of rat hepatocytes by glucocorticoid, cyclic adenosine 3',5'-monophosphate, and interleukin-6.
The effects of hormones and cytokines on angiotensinogen production were studied in primary cultured rat hepatocytes. The basal secretion of angiotensinogen decreased during culture. The addition of dexamethasone and (Bu)2cAMP completely prevented this decrease. Angiotensinogen secretion by freshly plated hepatocytes was slightly increased in response to dexamethasone, but after 24 h in culture, hepatocytes no longer responded to dexamethasone alone. When hepatocytes were treated with (Bu)2cAMP, glucagon, or forskolin, angiotensinogen secretion increased in response to dexamethasone in a concentration-dependent manner. 17 beta-Estradiol and T3 failed to stimulate angiotensinogen secretion in either the presence or absence of (Bu)2cAMP. Interleukin-6 (IL-6) exhibited a stimulatory activity on angiotensinogen secretion, which was dependent on the presence of dexamethasone, whereas IL-1 and tumor necrosis factor had no effect in either the presence or absence of dexamethasone and/or (Bu)2cAMP. Unlike primary cultured hepatocytes, angiotensinogen secretion by rat hepatoma H4IIEC3 cells increased in response to dexamethasone alone. This increase was not enhanced by (Bu)2cAMP, but was enhanced by IL-6. Thus, in primary cultures of rat hepatocytes, neither glucocorticoid, cAMP, nor IL-6 alone stimulated angiotensinogen production, but a combination of glucocorticoid and cAMP or of glucocorticoid and IL-6 exhibited a stimulatory activity on angiotensinogen production. These results suggest that angiotensinogen production in the liver is synergistically regulated by these factors, whereas the hepatoma cell line H4IIEC3 lacks the regulatory mechanism of cAMP on glucocorticoid-induced angiotensinogen production.
Ohtani
R
R
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Yayama
K
K
Takano
M
M
Itoh
N
N
Okamoto
H
H
D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005934:Glucagon / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D004273:DNA, Neoplasm; D004967:Estrogens; D005938:Glucocorticoids; D015850:Interleukin-6; D014284:Triiodothyronine; D000808:Angiotensinogen; D005576:Colforsin; D003994:Bucladesine; D003907:Dexamethasone; D004247:DNA; D005934:Glucagon; D000242:Cyclic AMP