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Inflammation Research

Erschienen in:

01.09.2011 | Original Research Paper

Folic acid inhibits lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages by suppressing MAPKs and NF-κB activation

verfasst von: Dan Feng, Yan Zhou, Min Xia, Jing Ma

Erschienen in: Inflammation Research | Ausgabe 9/2011

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Abstract

Objective

The aim of the present study was to investigate the effects of folic acid on the inflammatory responses to lipopolysaccharide (LPS) in RAW264.7 cells and the signal transduction pathways involved.

Methods

RAW264.7 macrophages were used. The production of nitric oxide (NO) was determined by the Griess test. The protein levels and mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were determined by ELISA and RT-PCR, respectively. The phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear nuclear factor-kappa B (NF-κB) p65 protein were analyzed by Western blotting.

Results

Folic acid inhibited LPS-induced production of NO, TNF-α and IL-1β with decreased mRNAs of inducible nitric oxide synthase (iNOS), TNF-α and IL-1β. Further study showed that folic acid inhibited the LPS-induced phosphorylation of MAPKs and the nuclear translocation of NF-κB.

Conclusion

Folic acid inhibits the inflammatory response of RAW 264.7 cells to LPS through inhibiting the MAPKs and NF-κB pathways.

Iyer R, Tomar SK. Folate: a functional food constituent. J Food Sci. 2009;74:R114–22.PubMedCrossRef

Hoffbrand AV, Weir DG. The history of folic acid. Br J Haematol. 2001;113:579–89.PubMedCrossRef

Scott JM, Weir DG. Folic acid, homocysteine and one-carbon metabolism: a review of the essential biochemistry. J Cardiovasc Risk. 1998;5:223–7.PubMedCrossRef

Wani NA, Hamid A, Kaur J. Folate status in various pathophysiological conditions. IUBMB Life. 2008;60:834–42.PubMedCrossRef

Gori T, Burstein JM, Ahmed S, Miner SE, Al-Hesayen A, Kelly S, et al. Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study. Circulation. 2001;104:1119–23.PubMedCrossRef

Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet. 2007;369:1876–82.PubMedCrossRef

Magni E, Bianchetti A, Rozzini R, Trabucchi M. Influence of nutritional intake on 6-year mortality in an Italian elderly population. J Nutr Elder. 1994;13:25–34.PubMedCrossRef

Imamura A, Murakami R, Takahashi R, Cheng XW, Numaguchi Y, Murohara T, et al. Low folate levels may be an atherogenic factor regardless of homocysteine levels in young healthy nonsmokers. Metabolism. 2010;59:728–33.PubMedCrossRef

Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567–77.PubMedCrossRef

10.

McCarty MF, Barroso-Aranda J, Contreras F. High-dose folate and dietary purines promote scavenging of peroxynitrite-derived radicals–clinical potential in inflammatory disorders. Med Hypotheses. 2009;73:824–34.PubMedCrossRef

11.

Title LM, Ur E, Giddens K, McQueen MJ, Nassar BA. Folic acid improves endothelial dysfunction in type 2 diabetes––an effect independent of homocysteine-lowering. Vasc Med. 2006;11:101–9.PubMedCrossRef

12.

Solini A, Santini E, Ferrannini E. Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects. Int J Obes (Lond). 2006;30:1197–202.CrossRef

13.

Chiarello PG, Penaforte FR, Japur CC, Souza CD, Vannucchi H, Troncon LE. Increased folate intake with no changes in serum homocysteine and decreased levels of C-reactive protein in patients with inflammatory bowel diseases. Dig Dis Sci. 2009;54:627–33.PubMedCrossRef

14.

Zhang R, Ma J, Xia M, Zhu H, Ling W. Mild hyperhomocysteinemia induced by feeding rats diets rich in methionine or deficient in folate promotes early atherosclerotic inflammatory processes. J Nutr. 2004;134:825–30.PubMed

15.

Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–74.PubMedCrossRef

16.

Laskin DL, Pendino KJ. Macrophages and inflammatory mediators in tissue injury. Annu Rev Pharmacol Toxicol. 1995;35:655–77.PubMedCrossRef

17.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.PubMedCrossRef

18.

Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [¹⁵N]nitrate in biological fluids. Anal Biochem. 1982;126:131–8.PubMedCrossRef

19.

Carter AB, Knudtson KL, Monick MM, Hunninghake GW. The p38 mitogen-activated protein kinase is required for NF-kappaB-dependent gene expression. The role of TATA-binding protein (TBP). J Biol Chem. 1999;274:30858–63.PubMedCrossRef

20.

Nakano H, Shindo M, Sakon S, Nishinaka S, Mihara M, Yagita H, et al. Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1. Proc Natl Acad Sci USA. 1998;95:3537–42.PubMedCrossRef

21.

Yea SS, Yang KH, Kaminski NE. Role of nuclear factor of activated T-cells and activator protein-1 in the inhibition of interleukin-2 gene transcription by cannabinol in EL4 T-cells. J Pharmacol Exp Ther. 2000;292:597–605.PubMed

22.

Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:471–9.PubMedCrossRef

23.

Detmers PA, Hernandez M, Mudgett J, Hassing H, Burton C, Mundt S, et al. Deficiency in inducible nitric oxide synthase results in reduced atherosclerosis in apolipoprotein E-deficient mice. J Immunol. 2000;165:3430–5.PubMed

24.

Beutler B. TNF, immunity and inflammatory disease: lessons of the past decade. J Investig Med. 1995;43:227–35.PubMed

25.

Gabay C, Lamacchia C, Palmer G. IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol. 2010;6:232–41.PubMedCrossRef

26.

Bluthgen N, Legewie S. Systems analysis of MAPK signal transduction. Essays Biochem. 2008;45:95–107.PubMedCrossRef

27.

Turjanski AG, Vaque JP, Gutkind JS. MAP kinases and the control of nuclear events. Oncogene. 2007;26:3240–53.PubMedCrossRef

28.

Ghosh S. Regulation of inducible gene expression by the transcription factor NF-kappaB. Immunol Res. 1999;19:183–9.PubMedCrossRef

29.

Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004;18:2195–224.PubMedCrossRef

Titel: Folic acid inhibits lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages by suppressing MAPKs and NF-κB activation
verfasst von: Dan Feng
Yan Zhou
Min Xia
Jing Ma
Publikationsdatum: 01.09.2011
Verlag: SP Birkhäuser Verlag Basel
Erschienen in: Inflammation Research / Ausgabe 9/2011
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-011-0337-2

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