Lipopolysaccharide (LPS) up-regulates the expression of haem oxygenase-1 in mouse placenta

Haem oxygenase-1 (HO-1) is an inducible enzyme that catalyses the rate-limiting step in the degradation of haem to biliverdin, carbon monoxide and iron. There is increasing evidence that HO plays important roles in the cellular defence against oxidative stress and the deleterious effects of pro-inflammatory cytokines. In the present study, we investigated the effects of lipopolysaccharide (LPS) on the expression of HO-1 in mouse placenta. When a single dose of LPS (75 microg/kg, i.p.) was administered to the pregnant mice, the expression of HO-1 in mouse placenta was markedly increased at 12 h after LPS treatment and remained elevated up to 48 h after LPS administration. The expression of HO-2, the constitutive form, did not change at the various time points observed. LPS-induced up-regulation of placental HO-1 was blocked after the pregnant mice were pre-treated with alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent. Correspondingly, PBN pre-treatment significantly inhibited LPS-induced lipid peroxidation and glutathione (GSH) depletion in mouse placenta. Furthermore, pentoxifylline (PTX), an inhibitor of tumour necrosis factor alpha (TNF-alpha) synthesis, also significantly attenuated LPS-induced up-regulation of placental HO-1. However, aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS), had little effect on LPS-induced up-regulation of HO-1 in mouse placenta. Taken together, these results indicate that LPS up-regulates the expression of HO-1 in mouse placenta. LPS-induced up-regulation of placental HO-1 is probably mediated, at least in part, by reactive oxygen species (ROS) and TNF-alpha, rather than nitric oxide.