Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription.
BACKGROUND: In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2) is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS). The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine.Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. METHODS: Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. RESULTS: The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti-oxidant, epigallocatechin gallate. CONCLUSION: Our results indicate that curcumin potently inhibits MIP-2 production at the level of gene transcription and offer further support for its potential use in the treatment of inflammatory conditions of the CNS.
Tomita
Michiyo
M
Department of Medicine, University of North Dakota School of Medicine & Health Sciences, 501 North Columbia Road, Grand Forks, ND 58201, USA. mtomita@medicine.nodak.edu.
Holman
Brita J
BJ
Santoro
Christopher P
CP
Santoro
Thomas J
TJ
Infect Immun. 1999 May;67(5):2590-601
10225925
J Neurochem. 2001 Nov;79(4):726-36
11723165
Science. 2003 Oct 31;302(5646):834-8
14593170
Eur J Immunol. 2000 Jul;30(7):1911-8
10940880
J Neurochem. 2002 Mar;80(5):824-34
11948246
Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005
11755008
Neuroscience. 1996 Sep;74(1):283-92
8843093
Eur J Pharmacol. 1999 Nov 19;384(2-3):191-5
10611441
Clin Cancer Res. 2004 Oct 15;10(20):6847-54
15501961
J Biol Chem. 2005 Feb 18;280(7):5892-901
15590663
J Biol Chem. 2003 Aug 1;278(31):28593-606
12771144
Phytother Res. 2002 Feb;16(1):36-42
11807963
Genomics. 1995 Dec 10;30(3):558-64
8825643
J Pharm Pharmacol. 1994 Dec;46(12):1013-6
7714712
Br J Pharmacol. 1999 Sep;128(2):380-4
10510448
Cancer Res. 1988 Nov 1;48(21):5941-6
3139287
J Exp Med. 1994 Oct 1;180(4):1445-56
7931077
Mol Med. 1998 Jun;4(6):376-83
10780880
J Exp Med. 1988 May 1;167(5):1713-8
3259258
J Neurosci Res. 2000 Jun 15;60(6):733-42
10861785
J Immunol. 2003 Dec 1;171(11):6072-9
14634121
Neuro Endocrinol Lett. 2003 Dec;24(6):469-73
15073579
J Neurosci. 2001 Nov 1;21(21):8370-7
11606625
J Pharm Pharmacol. 1997 Jan;49(1):105-7
9120760
Biochem Pharmacol. 2000 Dec 1;60(11):1665-76
11077049