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Inflammation Research

Erschienen in:

01.06.2010 | Original Research Paper

Sulforaphane suppresses LPS-induced inflammation in primary rat microglia

verfasst von: Lars-Ove Brandenburg, Markus Kipp, Ralph Lucius, Thomas Pufe, Christoph J. Wruck

Erschienen in: Inflammation Research | Ausgabe 6/2010

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Abstract

Objective and design

The aim of this study was to investigate the signal transduction pathways involved in sulforaphane (SF) mediated inhibition of the inflammatory response to lipopolysaccharide (LPS). Additionally, we investigated the effects of SF and LPS on the activity of Nrf2.

Material

Primary rat microglia and the murine microglia cell line BV2 were used.

Treatment

Cells were treated with LPS with or without SF.

Methods

Cell viability was measured via WST-assay. Real-time RT-PCR was performed to analyze cytokine mRNA levels. The nitric oxide (NO) release was measured in LPS-stimulated microglia. The induction of various signal transduction pathways and Nrf2 was determined by Western blotting. NF-κB and AP-1 activation was measured by dual luciferase assay.

Results

We showed that SF attenuates the LPS-induced increase of IL-1β, IL-6, and TNF-α expression in microglia. In addition, SF significantly decreases the NO in a concentration-dependent manner. SF inhibits LPS-stimulated ERK1/2 and JNK phosphorylation and thereby inhibits the LPS-induced activation of NF-κB- and activator protein-1 (AP-1). Moreover, SF and LPS together are able to induce Nrf2 activation.

Conclusions

We showed that SF, and also LPS by itself, are able to activate the cell’s defence against oxidative and electrophilic stress. We conclude that SF could be a candidate agent for anti-inflammatory treatment of the central nervous system.

Acs P, Kipp M, Norkute A, Johann S, Clarner T, Braun A, et al. 17beta-estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice. Glia. 2009;57:807–14.CrossRefPubMed

Braun A, Dang J, Johann S, Beyer C, Kipp M. Selective regulation of growth factor expression in cultured cortical astrocytes by neuro-pathological toxins. Neurochem Int. 2009;55:610–8.CrossRefPubMed

Kipp M, Beyer C. Impact of sex steroids on neuroinflammatory processes and experimental multiple sclerosis. Front Neuroendocrinol. 2009;30:188–200.CrossRefPubMed

Gonzalez-Scarano F, Martin-Garcia J. The neuropathogenesis of AIDS. Nat Rev Immunol. 2005;5:69–81.CrossRefPubMed

Gonsette RE. Neurodegeneration in multiple sclerosis: the role of oxidative stress and excitotoxicity. J Neurol Sci. 2008;274:48–53.CrossRefPubMed

Wilms H, Zecca L, Rosenstiel P, Sievers J, Deuschl G, Lucius R. Inflammation in Parkinson’s diseases and other neurodegenerative diseases: cause and therapeutic implications. Curr Pharm Des. 2007;13:1925–8.CrossRefPubMed

Brandenburg LO, Konrad M, Wruck C, Koch T, Pufe T, Lucius R. Involvement of formyl-peptide-receptor-like-1 and phospholipase D in the internalization and signal transduction of amyloid beta 1–42 in glial cells. Neuroscience. 2008;156:266–76.CrossRefPubMed

Thomas WE. Brain macrophages: evaluation of microglia and their functions. Brain Res Brain Res Rev. 1992;17:61–74.PubMed

Rock RB, Peterson PK. Microglia as a pharmacological target in infectious and inflammatory diseases of the brain. J Neuroimmune Pharmacol. 2006;1:117–26.CrossRefPubMed

10.

Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009;27:119–45.CrossRefPubMed

11.

Vallabhapurapu S, Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol. 2009;27:693–733.CrossRefPubMed

12.

Leong KG, Karsan A. Signaling pathways mediated by tumor necrosis factor alpha. Histol Histopathol. 2000;15:1303–25.PubMed

13.

Otten U, Marz P, Heese K, Hock C, Kunz D, Rose-John S. Cytokines and neurotrophins interact in normal and diseased states. Ann N Y Acad Sci. 2000;917:322–30.PubMedCrossRef

14.

Singh SV, Srivastava SK, Choi S, Lew KL, Antosiewicz J, Xiao D, et al. Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J Biol Chem. 2005;280:19911–24.CrossRefPubMed

15.

Zhang Y, Kensler TW, Cho CG, Posner GH, Talalay P. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci U S A. 1994;91:3147–50.CrossRefPubMed

16.

Zhang Y, Talalay P, Cho CG, Posner GH. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A. 1992;89:2399–403.CrossRefPubMed

17.

Heiss E, Herhaus C, Klimo K, Bartsch H, Gerhauser C. Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J Biol Chem. 2001;276:32008–15.CrossRefPubMed

18.

Lin W, Wu RT, Wu T, Khor TO, Wang H, Kong AN. Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway. Biochem Pharmacol. 2008;76:967–73.CrossRefPubMed

19.

Zhao J, Moore AN, Redell JB, Dash PK. Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury. J Neurosci. 2007;27:10240–8.CrossRefPubMed

20.

Heiss E, Gerhauser C. Time-dependent modulation of thioredoxin reductase activity might contribute to sulforaphane-mediated inhibition of NF-kappaB binding to DNA. Antioxid Redox Signal. 2005;7:1601–11.CrossRefPubMed

21.

Higgins LG, Kelleher MO, Eggleston IM, Itoh K, Yamamoto M, Hayes JD. Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents. Toxicol Appl Pharmacol. 2009;237:267–80.CrossRefPubMed

22.

Killeen ME, Englert JA, Stolz DB, Song M, Han Y, Delude RL, et al. The phase 2 enzyme inducers ethacrynic acid, DL-sulforaphane, and oltipraz inhibit lipopolysaccharide-induced high-mobility group box 1 secretion by RAW 264.7 cells. J Pharmacol Exp Ther. 2006;316:1070–9.CrossRefPubMed

23.

Jaiswal AK. Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med. 2004;36:1199–207.CrossRefPubMed

24.

Lee JM, Johnson JA. An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol. 2004;37:139–43.PubMed

25.

Wruck CJ, Claussen M, Fuhrmann G, Romer L, Schulz A, Pufe T, et al. Luteolin protects rat PC12 and C6 cells against MPP + induced toxicity via an ERK dependent Keap1-Nrf2-ARE pathway. J Neural Transm Suppl. 2007;72:57–67.CrossRefPubMed

26.

Wilms H, Rosenstiel P, Sievers J, Deuschl G, Zecca L, Lucius R. Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson’s disease. Faseb J. 2003;17:500–2.PubMed

27.

Brandenburg LO, Varoga D, Nicolaeva N, Leib SL, Wilms H, Podschun R, et al. Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis. J Neuropathol Exp Neurol. 2008;67:1041–54.CrossRefPubMed

28.

Brandenburg LO, Seyferth S, Wruck CJ, Koch T, Rosenstiel P, Lucius R, et al. Involvement of Phospholipase D 1 and 2 in the subcellular localization and activity of formyl-peptide-receptors in the human colonic cell line HT29. Mol Membr Biol. 2009;26:371–83.CrossRefPubMed

29.

Innamorato NG, Rojo AI, Garcia-Yague AJ, Yamamoto M, de Ceballos ML, Cuadrado A. The transcription factor Nrf2 is a therapeutic target against brain inflammation. J Immunol. 2008;181:680–9.PubMed

30.

Myzak MC, Dashwood WM, Orner GA, Ho E, Dashwood RH. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice. Faseb J. 2006;20:506–8.PubMed

31.

Yang LP, Zhu XA, Tso MO. Minocycline and sulforaphane inhibited lipopolysaccharide-mediated retinal microglial activation. Mol Vis. 2007;13:1083–93.PubMed

32.

Dinkova-Kostova AT, Massiah MA, Bozak RE, Hicks RJ, Talalay P. Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups. Proc Natl Acad Sci U S A. 2001;98:3404–9.CrossRefPubMed

33.

Thimmulappa RK, Scollick C, Traore K, Yates M, Trush MA, Liby KT, et al. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun. 2006;351:883–9.CrossRefPubMed

34.

Jeon YJ, Han SB, Ahn KS, Kim HM. Differential activation of murine macrophages by angelan and LPS. Immunopharmacology. 2000;49:275–84.CrossRefPubMed

35.

Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 2001;81:807–69.PubMed

Titel: Sulforaphane suppresses LPS-induced inflammation in primary rat microglia
verfasst von: Lars-Ove Brandenburg
Markus Kipp
Ralph Lucius
Thomas Pufe
Christoph J. Wruck
Publikationsdatum: 01.06.2010
Verlag: SP Birkhäuser Verlag Basel
Erschienen in: Inflammation Research / Ausgabe 6/2010
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-009-0116-5

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Abstract

Objective and design

Material

Treatment

Methods

Results

Conclusions

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