Transcriptional activation of heme oxygenase-1 gene in mouse spleen, liver and kidney cells after treatment with lipopolysaccharide or hemoglobin.

Heme oxygenase (HO)-1 catalyzes the conversion of heme to biliverdin, iron and carbon monoxide. HO-1 is induced by many reagents including heme, Hb and lipopolysaccharide (LPS). LPS is known to activate the HO-1 gene in cultured mouse liver and macrophage cells through oxidative activation of NF-kappaB. But little is known about the effect of LPS and Hb on the HO-1 gene in living organisms. To study this issue, we examined the HO-1 and its mRNA levels in mouse liver, spleen and kidney after intravenous administration of LPS and Hb. On LPS treatment, the amount of HO-1 and its mRNA increased markedly mainly in mouse spleen, but on Hb treatment the amounts of HO-1 and its mRNA increased slightly only in liver. Run-off transcription assay supported the above results and band shift assays also revealed that LPS significantly activates an NF-kappaB-like factor in spleen cells, while Hb slightly activates it in liver cells. According to our previous study, a small amount of Hb injected to mouse is selectively taken up by liver as Hb-haptoglobin complex. These results suggest different pathways for the HO gene activation in mouse organs; one by LPS in spleen cells and the other by Hb in liver cells.