Regulation of human Gc (vitamin D--binding) protein levels: hormonal and cytokine control of gene expression in vitro.
Studies were performed in Hep3B hepatocytes to better elucidate the mechanisms regulating circulating levels of human group-specific component (Gc). We measured changes in Gc messenger RNA (mRNA) synthesis and levels of secreted protein resulting from treatment of hepatocytes with cytokines and hormones known to influence synthesis of other proteins of hepatic origin. We particularly focused on compounds known to be prototypic stimulants during the acute phase response. Interleukin-6 (IL-6) and dexamethasone were shown to increase Gc mRNA approximately twofold while transforming growth factor beta (TGF beta) decreased Gc mRNA in a dose-dependent fashion by up to fivefold. The effects on secreted Gc protein levels were similar. These results indicate that Gc protein appears to be regulated differently than the other members of this gene family, albumin and alpha-fetoprotein (AFP), which are negative acute phase reactants. In addition, these contrasting effects on Gc synthesis of IL-6 and dexamethasone and of TGF beta suggest that high basal levels of Gc synthesis may be maintained during the acute phase response.
Guha
C
C
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston 29425, USA.
Osawa
M
M
Werner
P A
PA
Galbraith
R M
RM
Paddock
G V
GV
D000199:Actins / Q000096:biosynthesis; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012709:Serum Albumin / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014809:Vitamin D-Binding Protein / Q000032:analysis / Q000096:biosynthesis*; D000509:alpha-Fetoproteins / Q000096:biosynthesis
D000199:Actins; D000911:Antibodies, Monoclonal; D017931:DNA Primers; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D012709:Serum Albumin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D014809:Vitamin D-Binding Protein; D000509:alpha-Fetoproteins; D003907:Dexamethasone