Effect of nicotine on the release of lactate dehydrogenase and the production of tumor necrosis factor-α of cultured macrophage

Ding, Wen-mao; Li, Lan; Wang, Rui-ying; Cao, Zhu-ling

doi:10.5372/1905-7415.0603.065

Abstract

Background: Nicotine can affect the development of Atherosclerosis (AS). Monocytes/macrophages are the important cells hi the AS lesions.

Objective: We studied the mechanisms of smoking on AS. The effects of nicotine on macrophage were investigated hi this study.

Methods: Different concentration of nicotine (6 × 10^-9~-5 mol/L), different incubation time (3, 6, 9, 12, 18, and 24 horn s) and 7 β-hydroxycholesterol (50 μg ml) were schemed in this study. After exposure of macrophage to those different conditions, lactate dehydrogenase (LDH) activity and tumor necrosis factor-⃞ (TNF-α) content in the supernatant were assayed.

Results: Nicotine (6 × 10^-9mol/L~-6×10^-5mol/L) treatment resulted in a marked reduction of LDH in the supernatant (131,0±9.6 U/L. 129.7±6.2 U/L, 129.4±5.3 U/L, 134.2±8.4 U/L, and 138.3+9.7 U/L vs. 151.3+8.1 U/L, p <0.05 respectively, q-test). The same change trend was seen when co-treated with 7β-hydroxycholestrol and nicotine (135.7±7.6U/L, 135.6±6.6U/L, 136.1±6.7 U/L, 142.9±4.5 U/L, and 146.4±4.4 U/L vs. 152.4⃞6.2U/L, P<0.05 respectively, q-test). The peak effects occurred at the nicotine concentration of 6 × 10^-7mol/L and the first 18-hours incubation. Nicotine (6 ×10^-9mol/L~6 × 10^-6mol L) treatment result in the increase of TNF-α in the supernatant (0.28±0.06 ng/mL, 0.32±0.05 ng/mL, 0.40±0.07 ng/mL. and 0.30±0.08 ng/mL vs. 0.17±0.05 ng/mL, p <0.05 respectively, q-test). Nicotine (6 × 10^-5mol/L) treatment have no significant hicrease compared to the control group (0.21±0.08 ng/mL vs. 0.17+0.05 ng/mL, p >0.05, q-test). The peak effects occurred at the nicothie concentration of 6 × 10^-7mol/L.

Conclusions: Nicotine can produce the beneficial effect on macrophage. Nicotine treatment can activate macrophage to produce TNF-α. Thus, nicotine can be a mechanism on the development of atherosclerosis.

References

1. Report of the working Group of Arteriosclerosis of the National Heart Lung and Blood Institute. Washington DC. Government Printing Office; 1981.
Search in Google Scholar Back to article
2. Murray CJ and Lopez AD. Global mortality, disability and thecontribution of risk factors: Global Burden of Disease Study. Lancet. 1997; 349:1436-42.10.1016/S0140-6736(96)07495-8
Search in Google Scholar Back to article
3. Yan ZQ, Hansson GK. Innate immunity, macrophage activation, and atherosclerosis. Immunol Rev. 2007; 219:187-203.10.1111/j.1600-065X.2007.00554.x
Search in Google Scholar Back to article
4. Libby P. Inflammation in atherosclerosis. Nature. 2002; 420:868-74.10.1038/nature01323
Search in Google Scholar Back to article
5. Hansson GK, Libby P, Schonbeck U, Yan ZQ. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res. 2002; 91:281-91.10.1161/01.RES.0000029784.15893.10
Open DOI Search in Google Scholar Back to article
6. Zimmerman M, Mcgeachie J. The effect of nicotine on aortic endothelium: Aquantitative ultrastructural study. Atheroselerosis. 1987; 63:33.10.1016/0021-9150(87)90079-7
Search in Google Scholar Back to article
7. Suzuki N, Ishii Y, Kitamura S. Effects of nicotine on production of endothelium and eicosanoid by bovine pulmonary artery endothelial cells. Prostaglandins Leukot Essent Fatty Acids. 1994; 50:193.10.1016/0952-3278(94)90144-9
Search in Google Scholar Back to article
8. Aoshiba KN, Yasui S, Konno K. Nicotine prolongs neutrophil surrival by suppressing apoptosis. J Lan Clin Med. 1996; 127:186-94.10.1016/S0022-2143(96)90077-3
Search in Google Scholar Back to article
9. Cucina A, Fuso A, Coluccia P, Cavallaro A. Nicotine inhibits apoptosis and stimulates proliferation in aortic smooth muscle cells through a functional nicotinic acetylcholine receptor. J Surg Res. 2008; 150:227-35.10.1016/j.jss.2007.10.01918295799
Search in Google Scholar Back to article
10. Heeschen C, Jang JJ, Weis M, Pathak A, Kaji S, Hu RS, et al. Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. Nat Med. 2001; 7: 833-9.10.1038/8996111433349
Open DOI Search in Google Scholar Back to article
11. Kunio Yufu, Naohiko Takahashi, Norihiro Okada, Tetsuji Shinohara, Masahide Hara, Tetsunori Saikawa, et al. Influence of Systolic Blood Pressure and Cigarette Smoking on Endothelial Function in Young Healthy People. Circ J. 2009; 73:174-8.10.1253/circj.CJ-08-0467
Search in Google Scholar Back to article
12. Conklin BS, Zhao W, Zhong D, Chen C. Nicotine and cotinine Up-Regulate vascular endothelial growth factor expression in endothelial cells. Am J Pathology. 2002; 160:413-8.10.1016/S0002-9440(10)64859-6
Search in Google Scholar Back to article
13. Heeschen C, Weis M, Cooke JP. Nicotine promotes arteriogenesis. J AM Coll Cardiol. 2003; 41:489-96.10.1016/S0735-1097(02)02818-8
Search in Google Scholar Back to article
14. Chong IW, Lin SR, Hwang JJ, Huang MS, Wang TH, Hung JY, et al. Expression and regulation of the macrophage inflammatory protein-1 alpha gene by nicotine in rat alveolar macrophages. Eur Cytokine Netw. 2002; 13:242-9.
Search in Google Scholar Back to article
15. Sykes AP, Brampton C, Klee S, Chander CL, Whelan C, Parsons ME. An investigation into the effect and mechanisms of action of nicotine in inflammatory bowel disease. Inflamm Res. 2003; 49:311-9.10.1007/s000110050597
Search in Google Scholar Back to article
16. Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L,et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 2004; 10:1216-21.10.1038/nm1124
Search in Google Scholar Back to article
17. Saeed RW, Varma S, Peng-Nemeroff T, Sherry B, Balakhaneh D, Huston J,et al. Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med. 2004; 201: 1113-23.10.1084/jem.20040463
Search in Google Scholar Back to article
18. Guinet E, Yoshida K, Nouri-Shirazi M. Nicotine environment affects the differentiation and functional maturation of monocytes derived dendritic cells (DCs). Immunol Lett. 2004; 95:45-55.10.1016/j.imlet.2004.06.003
Open DOI Search in Google Scholar Back to article
19. Vassallo R, Tamada K, Lau JS, Kroening PR, Chen L. Cigarette smoke extract suppresses human dendritic cell function lea ding to preferential induction of Th-2 priming. J Immunol. 2005; 175:2684-91.10.4049/jimmunol.175.4.2684
Search in Google Scholar Back to article
20. Plaeger-Marsahall S, J.W. Smith. Experimental infection of subpopulations of human peripheral blood leukocytes by herpes simples virus. Proc. Soc. Exp. Biol. Med. 1978; 158:263-8.
Search in Google Scholar Back to article
21. Moreyra AE, Lacy CR, Wilson AC, Kumar A, Kostis JB. Arterial blood concentration and coronary vasconstrictive effect of low-nicotine cigarette smoking. Am Heart J. 1992; 124:392-7.10.1016/0002-8703(92)90603-S
Search in Google Scholar Back to article
22. Khosla S, Laddu A, Ehrenpreis S, Somberg JC. Cardiovascular effects of nicotine: Relation to deleterious effects of cigarette smoking. Am Heart J. 1993; 12:1669-74.
Search in Google Scholar Back to article
23. Lau PP, Li L, Merched AJ, Zhang AL, Ko KW, Chan L. Nicotine induces proinflammatory responses in macrophages and the aorta leading to acceleration of atherosclerosis in low-density lipoprotein receptor (-/-) mice. Arterioscler Thromb Vasc Biol. 2006; 2:143-9.10.1161/01.ATV.0000193510.19000.1016254210
Open DOI Search in Google Scholar Back to article
24. Wang Y, Wang L, Ai X, Zhao J, Hao X, Lu Y, et al. Nicotine could augment adhesion molecule expression in human endothelial cells through macrophages secreting TNF-α, IL-1β. Internation immunopharmacology. 2004; 4:1675-86.10.1016/j.intimp.2004.07.02815454119
Open DOI Search in Google Scholar Back to article
25. Suzuki J, Bayna E, Molle ED, Lew WYW. Nicotine inhibits cardiac apoptosis induced by lipopolysaccharide in rats. J Am Coll Cardiol. 2003; 41: 482-7.10.1016/S0735-1097(02)02820-6
Search in Google Scholar Back to article
26. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, et al. Nicotinic acetylcholine receptor a7 subunit is an essential regulator of inflammation. Nature. 2003, 421:384-8.10.1038/nature0133912508119
Search in Google Scholar Back to article
27. Yoshikawa H, Kurokawa M, Ozaki N, Nara K, Atou K, Takada E, et al. Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kB phosphorylation and nuclear factor-kB transcriptional activity through nicotinic acetylcholine receptor-a7. Clin Exp Immunol. 2006;146:116-23.10.1111/j.1365-2249.2006.03169.x180973516968406
Search in Google Scholar Back to article

Effect of nicotine on the release of lactate dehydrogenase and the production of tumor necrosis factor-α of cultured macrophage

Abstract

Paradigm

My account