Tumor necrosis factor-alpha and interferon-gamma inhibit insulin-like growth factor II gene expression in human fetal adrenal cell cultures.
Insulin-like growth factor-II (IGF-II) gene expression is induced by adrenocorticotropic hormone (ACTH) in human fetal adrenals (HFA), which suggests an important role for IGF-II in HFA growth and differentiation. Many cytokines have different regulatory actions in the endocrine glands. In the present study we have investigated the effects of two cytokines, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), on the regulation of IGF-II gene expression in cultured HFA cells. Both TNF-alpha and IFN-gamma inhibited basal and ACTH-induced accumulation of IGF-II mRNA dose-dependently. Cell viability was not altered by treatment with TNF-alpha or IFN-gamma. In addition, the combination of TNF-alpha and IFN-gamma decreased ACTH-induced IGF-II mRNAs more potently than each cytokine alone. Our results suggest that TNF-alpha and IFN-gamma may be involved in the regulation of HFA growth and differentiation via local IGF-II production.
Department of Pathology, University of Helsinki, Finland.
V
V
Ilvesmäki
M
M
Jäättelä
E
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Saksela
R
R
Voutilainen
D000311:Adrenal Glands / Q000196:embryology* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007335:Insulin-Like Growth Factor II; D007371:Interferon-gamma; D000324:Adrenocorticotropic Hormone