TY - JOUR
T1 - Cytokine induction of haem oxygenase mRNA in mouse liver
T2 - Interleukin 1 transcriptionally activates the haem oxygenase gene
AU - Rizzardini, M.
AU - Terao, M.
AU - Falciani, F.
AU - Cantoni, L.
PY - 1993
Y1 - 1993
N2 - Accumulation of the mRNA coding for haem oxygenase (HO, EC 1.14.99.3) was stimulated by treating mice with endotoxin (lipopolysaccharide, LPS; 20 μg/mouse intraperitoneally), suggesting that haem catabolism is a target of infection and inflammation in vivo. Therefore various cytokines, possible mediators for the biological responses to LPS, were administered intraperitoneally to mice, and the levels of HO mRNA were measured by Northern-blotting analysis using the rat HO cDNA as a probe. Marked induction of HO mRNA was observed 2 h after administration of interleukin 1 (IL-1) (34-fold) and tumour necrosis factor (19.5-fold) (5 μg/mouse), whereas interleukin 6 (6.2 μg/mouse) was much less active (3.5-fold) and interleukin 2 (25 μg/mouse) and interferon-γ (3 μg/mouse) were ineffective. HO mRNA induced by the cytokines or LPS accumulated rapidly (maximum at 1-2 h after administration), preceding the elevation of HO enzymic activity. Treatment of mice with IL-1 stimulated the transcription of the HO gene by 4-fold, as assessed by in vitro nuclear-run-on assay. These results indicate that enzymic haem catabolism in the liver is a process inducible in vivo by inflammatory cytokines, which up-regulate HO synthesis at the transcriptional level. Increased removal of haem might be part of the protective mechanisms elicited by the acute-phase response, possibly to reduce the pro-oxidant state of the cell.
AB - Accumulation of the mRNA coding for haem oxygenase (HO, EC 1.14.99.3) was stimulated by treating mice with endotoxin (lipopolysaccharide, LPS; 20 μg/mouse intraperitoneally), suggesting that haem catabolism is a target of infection and inflammation in vivo. Therefore various cytokines, possible mediators for the biological responses to LPS, were administered intraperitoneally to mice, and the levels of HO mRNA were measured by Northern-blotting analysis using the rat HO cDNA as a probe. Marked induction of HO mRNA was observed 2 h after administration of interleukin 1 (IL-1) (34-fold) and tumour necrosis factor (19.5-fold) (5 μg/mouse), whereas interleukin 6 (6.2 μg/mouse) was much less active (3.5-fold) and interleukin 2 (25 μg/mouse) and interferon-γ (3 μg/mouse) were ineffective. HO mRNA induced by the cytokines or LPS accumulated rapidly (maximum at 1-2 h after administration), preceding the elevation of HO enzymic activity. Treatment of mice with IL-1 stimulated the transcription of the HO gene by 4-fold, as assessed by in vitro nuclear-run-on assay. These results indicate that enzymic haem catabolism in the liver is a process inducible in vivo by inflammatory cytokines, which up-regulate HO synthesis at the transcriptional level. Increased removal of haem might be part of the protective mechanisms elicited by the acute-phase response, possibly to reduce the pro-oxidant state of the cell.
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M3 - Article
C2 - 8452519
AN - SCOPUS:0027534465
VL - 290
SP - 343
EP - 347
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 2
ER -