HO-1 as modulator of the innate immune response in pregnancy.

PROBLEM:The immune modulatory effect of heme oxygenase-1 (HO-1) is well documented in studies about sepsis and transplantation. This work evaluates the influence of HO-1 on the innate immune response during pregnancy. METHOD OF STUDY:Human first-trimester trophoblasts derived from normal pregnancies or spontaneous abortions were analyzed for their basal HO-1, BCL-associated athanogene-1 (Bag-1), and cytokine production before and after LPS treatment. In vivo, pregnant Hmox1+/+ and Hmox1+/- female mice were treated with LPS, and the production of Bag-1 was evaluated. RESULTS:Human trophoblasts up-regulated the expression of both HO-1 and pro-inflammatory cytokines after LPS treatment, whereas the basal level of HO-1 was higher in normal pregnancies. In vivo, HO-1 deficiency provoked diminished Bag-1 level upon LPS treatment. CONCLUSION:HO-1 deficiency causes an inflammatory immune reaction and diminished expression of protective molecules in trophoblasts. Thus, HO-1 emerges as one important modulator of innate immune responses in pregnancy.

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