Nicotine inhibits cytokine production by placenta cells via NFκB:: Potential role in pregnancy-induced hypertension
Nicotine inhibits cytokine production by placenta cells via NFκB:: Potential role in pregnancy-induced hypertension
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DOI：
10.2119/2007-00067.dowling
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发表时间：
2007-11-01
影响因子：
5.7
通讯作者：
Metz, Christine N.
中科院分区：
文献类型：
--
作者：
Dowling, Oonagh;Rochelson, Burton;Metz, Christine N.
妊娠高血压综合征(PIH)，又称先兆子痫，是导致孕产妇和胎儿死亡的主要原因之一。虽然妊高征的确切原因尚不清楚，但细胞因子的异常产生和胎盘的参与被认为是重要的因素。孕期吸烟被广泛认为对母亲和胎儿都有害，对妊高征有保护作用。基于香烟的主要成分尼古丁的抗炎活性，我们研究了尼古丁和其他胆碱能激动剂在体外对胎盘炎症反应的影响。我们观察到尼古丁和其他胆碱能激动剂在刺激后显著抑制胎盘细胞因子的产生。胎盘细胞表达α7烟碱型乙酰胆碱受体(α7nAChR)，利用胆碱能拮抗剂，我们证明尼古丁和其他胆碱能激动剂的抗炎作用部分是通过nAChR途径介导的。相反，胆碱能刺激对可溶性FMS样酪氨酸激酶(SFlt)的表达没有影响，sflt是一种与妊高征期母体血管功能障碍有关的抗血管生成物质。机制研究表明，胆碱能激动剂发挥抗炎作用的机制是，包括尼古丁在内的胆碱能激动剂可能通过核因子kappa B减少胎盘细胞产生的细胞因子来预防妊高征。
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.