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

Abstract 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 2 (0–50 μM) or CdCl 2 (25 μM) for different times. The pregnant mice were administered with CdCl 2 (3.0 mg/kg, i.p.) on GD15. Results TNF-α , IL-8 and IL-6 mRNAs were elevated in CdCl 2 -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 2 -exposed mice. Additional experiment showed that gestational Cd exposure activated Akt signaling in mouse placenta. Co-culture with CdCl 2 elevated pAkt level in JEG-3 cells in concentration- and time-dependent manners. LY294002, a specific inhibitor of PI3K, blocked CdCl 2 -evoked Akt phosphorylation in JEG-3 cells. Concomitantly, LY294002 inhibited CdCl 2 -induced IL-8 in JEG-3 cells. N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, blocked CdCl 2 -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.