Expression of heme oxygenase-1 is associated with abortion caused by Brucella abortus infection in pregnant mice

Brucella abortus is a facultative intracellular pathogen that can survive inside macrophages and trophoblast giant (TG) cells, and the causative agent of brucellosis. In the present study, we found that expression of heme oxygenase-1 (HO-1) in TG cells is correlated with abortion induced by B. abortus infection in pregnant mice. Expression of HO-1 in the placenta was decreased by B. abortus infection and treatment with cobalt-protoporphyrin (Co-PP), which is known to up-regulate HO-1 expression, inhibited abortion due to the bacterial infection. In TG cells, treatment with Co-PP was shown to up-regulate HO-1, whereas its expression was decreased by B. abortus infection. Such down-regulation of HO-1 in the TG cells was enhanced by IFN-γ treatment. HO-1 down-regulation in TG cells due to knockdown or IFN-γ treatment served to induce cell death caused by B. abortus infection. These results suggest that down-regulation of HO-1 in TG cells due to B. abortus infection is an important event in infectious abortion.