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

Abstract

IntroductionSeveral 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. MethodsHuman JEG-3 cells were treated with different concentration of CdCl2 (0–50 μM) or CdCl2 (25 μM) for different times. The pregnant mice were administered with CdCl2 (3.0 mg/kg, i.p.) on GD15. ResultsTNF-α, IL-8 and IL-6 mRNAs were elevated in CdCl2-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 CdCl2-exposed mice. Additional experiment showed that gestational Cd exposure activated Akt signaling in mouse placenta. Co-culture with CdCl2 elevated pAkt level in JEG-3 cells in concentration- and time-dependent manners. LY294002, a specific inhibitor of PI3K, blocked CdCl2-evoked Akt phosphorylation in JEG-3 cells. Concomitantly, LY294002 inhibited CdCl2-induced IL-8 in JEG-3 cells. N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, blocked CdCl2-evoked Akt phosphorylation in mouse placenta and human trophoblast cells. Additionally, NAC attenuated Cd-induced up-regulation of KC in amniotic fluid. DiscussionCd 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.