Cadmium induces inflammatory cytokines through activating Akt signaling in mouse placenta and human trophoblast cells.

Introduction: Several reports demonstrated that cadmium (Cd) had proinflammatory activities. The present study aimed to investigate whether Cd induces inflammatory cytokines in mouse placenta and human trophoblast cells.

Methods: Human JEG-3 cells were treated with different concentration of CdCl (0-50 μM) or CdCl (25 μM) for different times. The pregnant mice were administered with CdCl (3.0 mg/kg, i.p.) on GD15.

Results: TNF-α, IL-8 and IL-6 mRNAs were elevated in CdCl-treated JEG-3 cells. Several inflammatory cytokines were up-regulated in Cd-treated placenta of mice. Moreover, keratinocyte chemokine (KC), a functional analogue of human IL-8, was increased in maternal serum and amniotic fluid from CdCl-exposed mice. Additional experiment showed that gestational Cd exposure activated Akt signaling in mouse placenta. Co-culture with CdCl elevated pAkt level in JEG-3 cells in concentration- and time-dependent manners. LY294002, a specific inhibitor of PI3K, blocked CdCl-evoked Akt phosphorylation in JEG-3 cells. Concomitantly, LY294002 inhibited CdCl-induced IL-8 in JEG-3 cells. N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, blocked CdCl-evoked Akt phosphorylation in mouse placenta and human trophoblast cells. Additionally, NAC attenuated Cd-induced up-regulation of KC in amniotic fluid.

Discussion: Cd induces inflammatory cytokines partially through activating Akt signaling in mouse placenta and human trophoblast cells. NAC may be exploited for prevention of Cd-induced placental inflammation.