Lycopene suppresses LPS-induced NO and IL-6 production by inhibiting the activation of ERK, p38MAPK, and NF-kappaB in macrophages.
BACKGROUND
Lycopene has antioxidant, anticancer, and anti-inflammatory effects with molecular mechanisms not fully identified.


OBJECTIVE
We investigated the effects of lycopene on the inflammatory responses to lipopolysaccharide (LPS) in RAW264.7 cells and the signal transduction pathways involved.


RESULTS
Lycopene inhibited LPS-induced production of nitric oxide (NO) and interleukin-6 (IL-6) with decreased mRNAs of inducible nitric oxide synthase and IL-6 but had no effect on TNF-alpha. Further study showed that lycopene also inhibited LPS-induced IkappaB phosphorylation, IkappaB degradation, and NF-kappaB translocation. Moreover, lycopene blocked the phosphorylation of ERK1/2 and p38 MAP kinase but not c-Jun NH(2)-terminal kinase. To confirm the causal link between MAP kinase inhibition and its anti-inflammatory effects, we treated the cells with SB 203580 and U0126. These inhibitors significantly inhibited LPS-induced NO and IL-6 formation.


CONCLUSIONS
Lycopene inhibits the inflammatory response of RAW 264.7 cells to LPS through inhibiting ERK/p38 MAP kinase and the NF-kappaB pathway.
Feng
Dan
D
Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road 2, 510080 Guangzhou, People's Republic of China.
Ling
Wen-Hua
WH
Duan
Rui-Dong
RD
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D000077276:Lycopene; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000975:Antioxidants; D002070:Butadienes; D004791:Enzyme Inhibitors; D007093:Imidazoles; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; D009569:Nitric Oxide; D002338:Carotenoids; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D000077276:Lycopene
Immunol Invest. 2008;37(3):183-90
18389438
Essays Biochem. 2008;45:95-107
18793126
Anal Biochem. 1982 Oct;126(1):131-8
7181105
J Immunol Methods. 1983 Dec 16;65(1-2):55-63
6606682
Oncogene. 2007 May 14;26(22):3240-53
17496919
J Nutr. 2005 Mar;135(3):592-7
15735099
Biochem Biophys Res Commun. 2008 Sep 19;374(2):248-52
18638450
Genes Dev. 2004 Sep 15;18(18):2195-224
15371334
Exp Mol Med. 2005 Aug 31;37(4):323-34
16155409
Arthritis Res. 2002;4 Suppl 3:S233-42
12110143
Annu Rev Pharmacol Toxicol. 1995;35:655-77
7598511
J Nutr Biochem. 2009 Aug;20(8):577-85
18824341
J Biol Chem. 1999 Oct 22;274(43):30858-63
10521478
Nutr Cancer. 1998;31(3):199-203
9795972
Curr Drug Targets Inflamm Allergy. 2005 Aug;4(4):471-9
16101524
Arch Biochem Biophys. 1989 Nov 1;274(2):532-8
2802626
Int J Vitam Nutr Res. 2001 Nov;71(6):347-51
11840838
Eur J Pharmacol. 2008 May 31;586(1-3):275-82
18439578
Eur J Pharmacol. 2007 Dec 8;576(1-3):151-9
17698059
J Leukoc Biol. 2001 Jan;69(1):3-10
11200064
Nutr Cancer. 2007;58(2):171-7
17640163
Nitric Oxide. 2006 Aug;15(1):30-9
16517190
J Pharmacol Exp Ther. 2000 Feb;292(2):597-605
10640296
J Agric Food Chem. 2006 Apr 5;54(7):2563-6
16569044
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3537-42
9520401
J Biol Chem. 2000 Mar 10;275(10):7403-9
10702314
Exp Biol Med (Maywood). 2002 Nov;227(10):845-51
12424324
Eur J Pharmacol. 2007 Jul 2;566(1-3):192-9
17477920
Immunol Res. 1999;19(2-3):183-9
10493172
J Natl Cancer Inst. 1999 Feb 17;91(4):317-31
10050865
Exp Biol Med (Maywood). 2002 Nov;227(10):920-3
12424335
Mol Cell Biol. 1997 Nov;17(11):6274-82
9343388
FASEB J. 2005 Feb;19(2):272-4
15545302