Normal pregnancy is the controlled state of inflammation and this systemic inflammatory response is reported to be more intense in preeclampsia. The current study tested the hypothesis that maternal serum stimulates interleukin 6 (IL-6) production from endothelial cells and that nicotine inhibits these effects. Human umbilical vein endothelial cells (HUVECs) were incubated with or without 0.5% serum from healthy pregnant women at term (n = 5) and treated with or without nicotine (10-9 to 10-6 mol/L) in the presence of 0.5% serum. Cell survival was determined by colorimetric assay. Interleukin 6 concentration and nuclear transcription factor kappa B (NF-kB) activities were determined by enzyme-linked immunosorbent assay (ELISA)-based method. Interleukin 6 production by endothelial cells was significantly stimulated in the presence of maternal serum. Nicotine significantly preserved cell survival and suppressed IL-6 production from endothelial cells. Nicotine also significantly inhibited NF-kB activation in endothelial cells. Nicotine inhibited inflammatory reaction through NF-kB suppression in vitro model of maternal vascular endothelium, and this effect may be one of the explanations for the reduced risk of preeclampsia in smokers.
Redman CW, Sargent ILLatest advances in understanding preeclampsia. Science. 2005;308(5728):1592-1594.
3.
Roberts JMEndothelial dysfunction in preeclampsia. Semin Reprod Endocrinol . 1998;16(1):5-15.
4.
Wang Y., Lewis DF, Alexander JS, Granger DNEndothelial barrier function in preeclampsia. Front Biosci . 2007;12: 2412-2424.
5.
Challis JR, Lockwood CJ, Myatt L., Norman JE, Strauss JF 3rd, Petraglia F.Inflammation and pregnancy. Reprod Sci. 2009 ;16(2):206-215.
6.
Borzychowski AM, Sargent IL, Redman CWInflammation and pre-eclampsia. Semin Fetal Neonatal Med. 2006;11(5): 309-316.
7.
Redman CW, Sargent ILPlacental stress and pre-eclampsia: a revised view. Placenta . 2009;30(suppl A):S38-S42.
8.
Austgulen R. , Lien E., Liabakk NB, Jacobsen G., Arntzen KJIncreased levels of cytokines and cytokine activity modifiers in normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 1994; 57(3):149-155.
9.
Greer IA, Lyall F., Perera T., Boswell F., Macara LMIncreased concentrations of cytokines interleukin-6 and interleukin-1 receptor antagonist in plasma of women with preeclampsia: a mechanism for endothelial dysfunction? Obstet Gynecol. 1994;84(6):937-940.
10.
Takacs P., Green KL, Nikaeo A., Kauma SWIncreased vascular endothelial cell production of interleukin-6 in severe preeclampsia. Am J Obstet Gynecol. 2003;188(3):740-744.
11.
Kauma SW, Wang Y., Walsh SWPreeclampsia is associated with decreased placental interleukin-6 production . J Soc Gynecol Investig. 1995;2(4):614-617.
12.
Conde-Agudelo A., Althabe F., Belizán JM, Kafury-Goeta ACCigarette smoking during pregnancy and risk of preeclampsia: a systematic review. Am J Obstet Gynecol. 1999;181(4): 1026-1035.
13.
Hammoud AO, Bujold E., Sorokin Y., Schild C., Krapp M., Baumann P.Smoking in pregnancy revisited: findings from a large population-based study . Am J Obstet Gynecol. 2005; 192(6):1856-1862.
14.
Lain KY, Wilson JW, Crombleholme WR, Ness RB, Roberts JMSmoking during pregnancy is associated with alterations in markers of endothelial function. Am J Obstet Gynecol. 2003;189(4):1196-1201.
15.
Wang H., Yu M., Ochani M., et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature. 2003;421(6921):384-388.
16.
Wang H., Liao H., Ochani M., et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 2004;10(11):1216-1221.
17.
Matthay MA, Ware LB: Can nicotine treat sepsis?Nat Med. 2004; 10(11): 1161-2, 2001;15(2):279-81.
18.
Saeed RW, Varma S., Peng-Nemeroff T., et al. Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med. 2005;201(7): 1113-1123.
19.
Speer P., Zhang Y., Gu Y., Lucas MJ, Wang Y.Effects of nicotine on intercellular adhesion molecule expression in endothelial cells and integrin expression in neutrophils in vitro. Am J Obstet Gynecol. 2002;186(3):551-556.
20.
Walsh SWObesity: a risk factor for preeclampsia. Trends Endocrinol Metab. 2007;18(10):365-370.
21.
Retnakaran R., Hanley AJ, Raif N., Connelly PW, Sermer M., Zinman B.C-reactive protein and gestational diabetes: the central role of maternal obesity. J Clin Endocrinol Metab . 2003;88(8):3507-3512.
22.
Shah TJ, Walsh SWActivation of NF-kB and expression of COX-2 in association with neutrophil infiltration in systemic vascular tissue of women with preeclampsia. Am J Obstet Gynecol. 2007; 196(1): 48,e1-8.
23.
Takacs P., Kauma SW, Sholley MM, Walsh SW, Dinsmoor MJ, Green K.Increased circulating lipid peroxides in severe preeclampsia activates NF-kB and upregulate ICAM-1 in vascular endothelial cells. FASEB J. 2001;15:279-281.
24.
Libermann TA , Baltimore D. Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol. 1990;10(5):2327-2334.
25.
Ng MK, Wu J., Chang E., Wang BY, Katzenberg-Clark R., Ishii-Watabe A., Cooke JPA central role for nicotinic cholinergic regulation of growth factor-induced endothelial cell migration. Arterioscler Thromb Vasc Biol . 2007;27(1): 106-112.
26.
Heeschen C. , Jang JJ, Weis M., et al. Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. Nat Med. 2001;7(7):833-839.
27.
Suzuki N., Ishii Y., Kitamura S.Effects of nicotine on production of endothelin and eicosanoid by bovine pulmonary artery endothelial cells. Prostaglandins Leukot Essent Fatty Acids. 1994; 50(4):193-197.
28.
Heeschen C. , Weis M., Aicher A., Dimmeler S., Cooke JPA novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine receptors. J Clin Invest. 2002;110(4):527-536.
29.
Darby TD, McNamee JE, van Rossum JMCigarette smoking pharmacokinetics and its relationship to smoking behavior . Clin Pharmacokinet. 1984;9:435-449.
30.
Cucina A., Corvino V., Sapienza P., et al. Nicotine regulates basic fibroblastic growth factor and transforming growth factor β1 production in endothelial cells. Biochem Biophys Res Commun. 1999;257(2):306-312.
31.
Conklin BS, Zhao W., Zhong DS, Chen C.Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells. Am J Pathol. 1984;9(5): 435-45.
32.
Mimura K., Tomimatsu T., Sharentuya N., Tskitishvili E., Kinugasa-Taniguchi Y., Kanagawa T., Kimura T.Nicotine restores endothelial dysfunction caused by excess sFlt1 and sEng in in vitro model of preeclamptic vascular endothelium: a possible therapeutic role of nicotinic acetylcholine receptor (nAChR) agonists for preeclampsia . Am J Obstet Gynecol. 2010; in press.
33.
Maynard S., Epstein FH, Karumanchi SAPreeclampsia and angiogenic imbalance. Annu Rev Med. 2008;59:61-78.
34.
Baum M., Schiff E., Kreiser D., et al. End-tidal carbon monoxide measurements in women with pregnancy-induced hypertension and preeclampsia. Am J Obstet Gynecol. 2000; 183(4):900-903.
35.
Dowling O., Rochelson B., Way K., Al-Abed Y., Metz CNNicotine inhibits cytokine production by placenta cells via NFkappaB: potential role in pregnancy-induced hypertension. Mol Med. 2007;13(11-12):576-583.
36.
Mehendale R., Hibbard J., Fazleabas A., Leach R.Placental angiogenesis markers sFlt-1 and PlGF: response to cigarette smoke . Am J Obstet Gynecol. 2007;197(4):363:e1-e5.
37.
Jeyabalan A. , Powers RW, Durica AR, Harger GF, Roberts JM, Ness RBCigarette smoke exposure and angiogenic factors in pregnancy and preeclampsia. Am J Hypertens. 2008;21(8):943-947.
38.
McGrath J., McDonald JW, Macdonald JKTransdermal nicotine for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2004;4:CD004722.
39.
Ogburn PL, Hurt RD, Croghan IT, et al. Nicotine pathch use in pregnant smokers: Nicotine and cotinine levels and fetal effects. Am J Obset Gynecol. 1999;181(3):736-743.
40.
Wisborg K., Henriksen TB, Jespersen LB, Secher NJNicotine patches for pregnant smokers: a randomized controlled study. Obstet Gynecol. 2000;96(6):967-971.
41.
Oncken C., Dornelas E., Greene J., et al. Nicotine gum for pregnant smokers: a randomized controlled trial . Obstet Gynecol. 2008;112(4):859-867.
42.
Strandberg-Larsen K., Tinggaard M., Nybo Andersen AM, Olsen J., Grønbaek M.Use of nicotine replacement therapy during pregnancy and stillbirth: a cohort study. BJOG. 2008;115(11):1405-1410.
43.
Ernst M., Moolchan ET, Robinson MLBehavioral and neural consequences of prenatal exposure to nicotine. J Am Acad Child Adolesc Psychiatry. 2001;40(6):630-641.
44.
Slotkin TAIf nicotine is a developmental neurotoxicant in animal studies, dare we recommend nicotine replacement therapy in pregnant women and adolescents? Neurotoxicol Teratol. 2008;30(1):1-19.
45.
Jonge W., Ulloa L.The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pathol. 2007; 151(7):915-929.
46.
Peltier MR, Ananth CVIs the association of maternal smoking and pregnancy-induced hypertension dependent on fetal growth?Am J Obstet Gynecol. 2007;196(6):532.e1-532.e6.
47.
Bouys D., Hospers G., Meijer C., Molema G., Mulder NHEndothelium in vitro: a review of human vascular endothelial cell lines for blood vessel-related research. Angiogenesis. 2001; 4(2):91-102.
48.
Bachetti T. , Morbidelli L.Endothelial cells in culture: a model for studying vascular functions. Pharmacol Res. 2000;42(1):9-19.
