Nicotine inhibits cytokine production by placenta cells via NFκB:: Potential role in pregnancy-induced hypertension

Pregnancy-induced hypertension (PIH), also known as preeclampsia, is one of the major causes of maternal and fetal death. While the precise cause of PIH is not known, aberrant cytokine production and placenta participation are considered to be important factors. Gestational cigarette smoking, which is widely accepted to be harmful to both the mother and fetus, is protective against PIH. Based on the anti-inflarnmatory activity of nicotine, the major component of cigarettes, we examined the effect of nicotine and other cholinergic agonists on placental inflammatory responses ex vivo. We observed that nicotine and other cholinergic agonists significantly suppress placenta cytokine production following stimulation. Placenta cells express the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR), and using cholinergic antagonists, we demonstrated that the anti-inflammatory effect of nicotine and other cholinergic agonists is, in part, mediated through the nAChR pathway. By contrast, cholinergic stimulation had no effect on the expression of soluble fms-like tyrosine kinase (sFlt), an antiangiogenic substance implicated in maternal vascular dysfunction during PIH Mechanistic studies reveal that cholinergic agonists exert their anti-inflammatory effects through the that cholinergic agonists, including nicotine, may reduce cytokine production by placenta cells via NF kappa B to protect against PIH.