Activation of the cholinergic anti-inflammatory pathway by nicotine ameliorates lipopolysaccharide-induced preeclampsia-like symptoms in pregnant rats.

INTRODUCTION: Preeclampsia (PE) exerts a more intense systemic inflammatory response than normal pregnancy. Recently, the role of the cholinergic anti-inflammatory pathway (CAP) in regulating inflammation has been extensively studied. The aim of this study was to investigate the effect of nicotine, a selective cholinergic agonist, on lipopolysaccharide (LPS)-induced preeclampsia-like symptoms in pregnant rats and to determine the molecular mechanism underlying it.

METHODS: Rats were administered LPS (1.0 μg/kg) via tail vein injection on gestational day 14 to induce preeclampsia-like symptoms. Nicotine (1.0 mg/kg/d) and α-bungarotoxin (1.0 μg/kg/d) were injected subcutaneously into the rats from gestational day 14-19. Clinical symptoms were recorded. Serum and placentas were collected to determine cytokine levels using Luminex. The mRNA and protein expression levels of α7 nicotinic acetylcholine receptor (α7nAChR) were determined using Real time-PCR and Western blot analysis. Immunohistochemistry was performed to determine the level of activation of nuclear factor-κB (NF-κB) in placentas.

RESULTS: Nicotine significantly ameliorated LPS-induced preeclampsia-like symptoms in pregnant rats (P < 0.05). Nicotine treatment decreased the levels of LPS-induced pro-inflammatory cytokines in the serum (P < 0.05) and placenta (P < 0.05). Nicotine significantly increased the expression of α7nAChR (P < 0.01) and attenuated the activation of NF-κB p65 in the placenta in LPS-induced preeclampsia (P < 0.01). Meanwhile, these protective effects of nicotine were abolished by the administration of the cholinergic antagonist α-bungarotoxin in preeclampsia rats.

DISCUSSION: Our findings suggest that the activation of α7nAChR by nicotine attenuates preeclampsia-like symptoms, and this protective effect is likely the result of the inhibition of inflammation via the NF-κB p65 pathway.