The human inter-alpha-trypsin inhibitor genes respond differently to interleukin-6 in HepG2 cells.
The effects of interleukin 6 (IL-6), the major inducer of the acute-phase reaction, on the expression of inter-alpha-trypsin inhibitor (ITI) genes were examined using human HepG2 hepatoma cells. The three ITI heavy-chain genes H1, H2 and H3 were transcriptionally regulated by IL-6 in a dose- and time-dependent manner. The treatment of HepG2 cells with IL-6 resulted in an increase of H1 and H3 mRNA levels and a decrease of H2 and L mRNA levels. Actinomycin D blocked the action of IL-6, suggesting that IL-6 regulated the H1, H2, H3 gene expression. Moreover, the kinetics of the ITI mRNA degradation in untreated and IL-6-treated cells confirmed these data. The nuclear run-on assay supports the regulatory effect of IL-6 at the transcription level of the L and H2 genes. Primer extension experiments showed that the effect of IL-6 on L, H2 and H3 mRNA synthesis was not related to the transcription starting point. Although H1, H2, H3 and L gene products are supposedly present in similar amounts in the ITI and pre-alpha-trypsin inhibitor molecules, the present work shows that these genes are regulated in a different manner, at least under the influence of IL-6.
Sarafan
N
N
Laboratoire de Physiopathologie et Génétique Rénale et Pulmonaire, l'Université de Rouen, Faculté de Médecine de Rouen, France.
Martin
J P
JP
Bourguignon
J
J
Borghi
H
H
Callé
A
A
Sesboüé
R
R
Diarra-Mehrpour
M
M
D000510:Alpha-Globulins / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D017077:Culture Media, Conditioned; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014361:Trypsin Inhibitors / Q000235:genetics*
D000510:Alpha-Globulins; D017077:Culture Media, Conditioned; D017931:DNA Primers; D015850:Interleukin-6; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D003609:Dactinomycin; C011877:inter-alpha-inhibitor; D004247:DNA