Naringenin Suppresses Neuroinflammatory Responses Through Inducing Suppressor of Cytokine Signaling 3 Expression
详细信息 查看全文
- 作者：Ling-Hsuan Wu ; Chingju Lin ; Hsiao-Yun Lin ; Yu-Shu Liu…
- 关键词：Neuroinflammation ; Microglia ; CNS ; Naringenin ; SOCS ; 3
- 刊名：Molecular Neurobiology
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：53
- 期：2
- 页码：1080-1091
- 全文大小：4,922 KB
- 参考文献：1.Ferrini F, De Koninck Y (2013) Microglia control neuronal network excitability via BDNF signalling. Neural Plast 2013:429815. doi:10.1155/2013/429815 PubMedCentral PubMed
2.Lin HY, Huang BR, Yeh WL, Lee CH, Huang SS, Lai CH, Lin H, Lu DY (2014) Antineuroinflammatory effects of lycopene via activation of adenosine monophosphate-activated protein kinase-alpha1/heme oxygenase-1 pathways. Neurobiol Aging 35(1):191–202. doi:10.1016/j.neurobiolaging.2013.06.020 CrossRef PubMed
3.Amor S, Peferoen LA, Vogel DY, Breur M, van der Valk P, Baker D, van Noort JM (2014) Inflammation in neurodegenerative diseases—an update. Immunology 142(2):151–166. doi:10.1111/imm.12233 PubMedCentral CrossRef PubMed
4.Inagaki-Ohara K, Kondo T, Ito M, Yoshimura A (2013) SOCS, inflammation, and cancer. JAKSTAT 2(3):e24053. doi:10.4161/jkst.24053 PubMedCentral PubMed
5.Baker BJ, Akhtar LN, Benveniste EN (2009) SOCS1 and SOCS3 in the control of CNS immunity. Trends Immunol 30(8):392–400. doi:10.1016/j.it.2009.07.001 PubMedCentral CrossRef PubMed
6.Gao A, Van Dyke TE (2014) Role of suppressors of cytokine signaling 3 in bone inflammatory responses. Front Immunol 4:506. doi:10.3389/fimmu.2013.00506 PubMedCentral CrossRef PubMed
7.Li Y, de Haar C, Peppelenbosch MP, van der Woude CJ (2012) SOCS3 in immune regulation of inflammatory bowel disease and inflammatory bowel disease-related cancer. Cytokine Growth Factor Rev 23(3):127–138. doi:10.1016/j.cytogfr.2012.04.005 CrossRef PubMed
8.Qin H, Roberts KL, Niyongere SA, Cong Y, Elson CO, Benveniste EN (2007) Molecular mechanism of lipopolysaccharide-induced SOCS-3 gene expression in macrophages and microglia. J Immunol 179(9):5966–5976CrossRef PubMed
9.Lu DY, Huang BR, Yeh WL, Lin HY, Huang SS, Liu YS, Kuo YH (2013) Anti-neuroinflammatory effect of a novel caffeamide derivative, KS370G, in microglial cells. Mol Neurobiol 48(3):863–874. doi:10.1007/s12035-013-8474-y CrossRef PubMed
10.Ronnett GV, Ramamurthy S, Kleman AM, Landree LE, Aja S (2009) AMPK in the brain: its roles in energy balance and neuroprotection. J Neurochem 109(Suppl 1):17–23. doi:10.1111/j.1471-4159.2009.05916.x PubMedCentral CrossRef PubMed
11.Giri S, Nath N, Smith B, Viollet B, Singh AK, Singh I (2004) 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside inhibits proinflammatory response in glial cells: a possible role of AMP-activated protein kinase. J Neurosci 24(2):479–487. doi:10.1523/JNEUROSCI. 4288-03.2004 CrossRef PubMed
12.Chen Z, Forman LW, Williams RM, Faller DV (2014) Protein kinase C-delta inactivation inhibits the proliferation and survival of cancer stem cells in culture and in vivo. BMC Cancer 14(1):90. doi:10.1186/1471-2407-14-90 PubMedCentral CrossRef PubMed
13.Kim BC, Jeon WK, Hong HY, Jeon KB, Hahn JH, Kim YM, Numazawa S, Yosida T, Park EH, Lim CJ (2007) The anti-inflammatory activity of Phellinus linteus (Berk. & M.A. Curt.) is mediated through the PKCdelta/Nrf2/ARE signaling to up-regulation of heme oxygenase-1. J Ethnopharmacol 113(2):240–247. doi:10.1016/j.jep.2007.05.032 CrossRef PubMed
14.Han YS, Zheng WH, Bastianetto S, Chabot JG, Quirion R (2004) Neuroprotective effects of resveratrol against beta-amyloid-induced neurotoxicity in rat hippocampal neurons: involvement of protein kinase C. Br J Pharmacol 141(6):997–1005. doi:10.1038/sj.bjp.0705688 PubMedCentral CrossRef PubMed
15.Yang MS, Lee J, Ji KA, Min KJ, Lee MA, Jou I, Joe E (2004) Thrombin induces suppressor of cytokine signaling 3 expression in brain microglia via protein kinase Cdelta activation. Biochem Biophys Res Commun 317(3):811–816. doi:10.1016/j.bbrc.2004.03.118 CrossRef PubMed
16.Bair AM, Thippegowda PB, Freichel M, Cheng N, Ye RD, Vogel SM, Yu Y, Flockerzi V, Malik AB, Tiruppathi C (2009) Ca2+ entry via TRPC channels is necessary for thrombin-induced NF-kappaB activation in endothelial cells through AMP-activated protein kinase and protein kinase Cdelta. J Biol Chem 284(1):563–574. doi:10.1074/jbc.M803984200 PubMedCentral CrossRef PubMed
17.Park JH, Jin CY, Lee BK, Kim GY, Choi YH, Jeong YK (2008) Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells. Food Chem Toxicol 46(12):3684–3690. doi:10.1016/j.fct.2008.09.056 CrossRef PubMed
18.Arul D, Subramanian P (2013) Naringenin (citrus flavonone) induces growth inhibition, cell cycle arrest and apoptosis in human hepatocellular carcinoma cells. Pathol Oncol Res 19(4):763–770. doi:10.1007/s12253-013-9641-1 CrossRef PubMed
19.Park HY, Kim GY, Choi YH (2012) Naringenin attenuates the release of pro-inflammatory mediators from lipopolysaccharide-stimulated BV2 microglia by inactivating nuclear factor-kappaB and inhibiting mitogen-activated protein kinases. Int J Mol Med 30(1):204–210. doi:10.3892/ijmm.2012.979 PubMed
20.Vafeiadou K, Vauzour D, Lee HY, Rodriguez-Mateos A, Williams RJ, Spencer JP (2009) The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury. Arch Biochem Biophys 484(1):100–109. doi:10.1016/j.abb.2009.01.016 CrossRef PubMed
21.Raza SS, Khan MM, Ahmad A, Ashafaq M, Islam F, Wagner AP, Safhi MM (2013) Neuroprotective effect of naringenin is mediated through suppression of NF-kappaB signaling pathway in experimental stroke. Neuroscience 230:157–171. doi:10.1016/j.neuroscience.2012.10.041 CrossRef PubMed
22.Huang BR, Tsai CF, Lin HY, Tseng WP, Huang SS, Wu CR, Lin C, Yeh WL, Lu DY (2013) Interaction of inflammatory and anti-inflammatory responses in microglia by Staphylococcus aureus-derived lipoteichoic acid. Toxicol Appl Pharmacol 269(1):43–50. doi:10.1016/j.taap.2013.03.004 CrossRef PubMed
23.Chuang JY, Chang PC, Shen YC, Lin C, Tsai CF, Chen JH, Yeh WL, Wu LH, Lin HY, Liu YS, Lu DY (2014) Regulatory effects of fisetin on microglial activation. Molecules 19(7):8820–8839. doi:10.3390/molecules19078820 CrossRef PubMed
24.Lin HY, Yeh WL, Huang BR, Lin C, Lai CH, Lin H, Lu DY (2012) Desipramine protects neuronal cell death and induces heme oxygenase-1 expression in Mes23.5 dopaminergic neurons. PLoS One 7(11):e50138. doi:10.1371/journal.pone.0050138 PubMedCentral CrossRef PubMed
25.Lu DY, Chen JH, Tan TW, Huang CY, Yeh WL, Hsu HC (2013) Resistin protects against 6-hydroxydopamine-induced cell death in dopaminergic-like MES23.5 cells. J Cell Physiol 228(3):563–571. doi:10.1002/jcp.24163 CrossRef PubMed
26.Lu DY, Tang CH, Chen YH, Wei IH (2010) Berberine suppresses neuroinflammatory responses through AMP-activated protein kinase activation in BV-2 microglia. J Cell Biochem 110(3):697–705. doi:10.1002/jcb.22580 CrossRef PubMed
27.Wiejak J, Dunlop J, Gao S, Borland G, Yarwood SJ (2012) Extracellular signal-regulated kinase mitogen-activated protein kinase-dependent SOCS-3 gene induction requires c-Jun, signal transducer and activator of transcription 3, and specificity protein 3 transcription factors. Mol Pharmacol 81(5):657–668. doi:10.1124/mol.111.076976 CrossRef PubMed
28.Miah MA, Choi SS, Lee SH (2012) Blueberry inhibits LPS-induced murine microglia cell activation and cell death. Bangl J Vet Med 10(1&2):87–92
29.Martinez FO (2011) Regulators of macrophage activation. Eur J Immunol 41(6):1531–1534. doi:10.1002/eji.201141670 CrossRef PubMed
30.Boche D, Perry VH, Nicoll JA (2013) Review: activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol 39(1):3–18. doi:10.1111/nan.12011 CrossRef PubMed
31.Qin H, Wilson CA, Roberts KL, Baker BJ, Zhao X, Benveniste EN (2006) IL-10 inhibits lipopolysaccharide-induced CD40 gene expression through induction of suppressor of cytokine signaling-3. J Immunol 177(11):7761–7771CrossRef PubMed
32.Matsuura H, Sakaue M, Subbaramaiah K, Kamitani H, Eling TE, Dannenberg AJ, Tanabe T, Inoue H, Arata J, Jetten AM (1999) Regulation of cyclooxygenase-2 by interferon gamma and transforming growth factor alpha in normal human epidermal keratinocytes and squamous carcinoma cells. Role of mitogen-activated protein kinases. J Biol Chem 274(41):29138–29148CrossRef PubMed
33.Uto T, Fujii M, Hou DX (2007) Effects of 6-(methylsulfinyl)hexyl isothiocyanate on cyclooxygenase-2 expression induced by lipopolysaccharide, interferon-gamma and 12-O-tetradecanoylphorbol-13-acetate. Oncol Rep 17(1):233–238PubMed
34.Giroux M, Descoteaux A (2000) Cyclooxygenase-2 expression in macrophages: modulation by protein kinase C-alpha. J Immunol 165(7):3985–3991CrossRef PubMed
35.Palmer DC, Restifo NP (2009) Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function. Trends Immunol 30(12):592–602. doi:10.1016/j.it.2009.09.009 PubMedCentral CrossRef PubMed
36.Auernhammer CJ, Melmed S (2001) The central role of SOCS-3 in integrating the neuro-immunoendocrine interface. J Clin Invest 108(12):1735–1740. doi:10.1172/JCI14662 PubMedCentral CrossRef PubMed
37.Akifusa S, Kamio N, Shimazaki Y, Yamaguchi N, Nonaka K, Yamashita Y (2010) Involvement of the JAK-STAT pathway and SOCS3 in the regulation of adiponectin-generated reactive oxygen species in murine macrophage RAW 264 cells. J Cell Biochem 111(3):597–606. doi:10.1002/jcb.22745 CrossRef PubMed
38.Alexander WS (2002) Suppressors of cytokine signalling (SOCS) in the immune system. Nat Rev Immunol 2(6):410–416. doi:10.1038/nri818 PubMed
39.Babon JJ, Nicola NA (2012) The biology and mechanism of action of suppressor of cytokine signaling 3. Growth Factors 30(4):207–219. doi:10.3109/08977194.2012.687375 PubMedCentral CrossRef PubMed
40.Linke A, Goren I, Bosl MR, Pfeilschifter J, Frank S (2010) Epithelial overexpression of SOCS-3 in transgenic mice exacerbates wound inflammation in the presence of elevated TGF-beta1. J Invest Dermatol 130(3):866–875. doi:10.1038/jid.2009.345 CrossRef PubMed
41.Cacalano NA, Sanden D, Johnston JA (2001) Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras. Nat Cell Biol 3(5):460–465. doi:10.1038/35074525 CrossRef PubMed
42.Lee IT, Lin CC, Lee CY, Hsieh PW, Yang CM (2013) Protective effects of (-)-epigallocatechin-3-gallate against TNF-alpha-induced lung inflammation via ROS-dependent ICAM-1 inhibition. J Nutr Biochem 24(1):124–136. doi:10.1016/j.jnutbio.2012.03.009 CrossRef PubMed
43.Wiejak J, Dunlop J, Mackay SP, Yarwood SJ (2013) Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells. Biochem J 454(2):283–293. doi:10.1042/BJ20130481 PubMedCentral CrossRef PubMed
44.Lovren F, Pan Y, Quan A, Szmitko PE, Singh KK, Shukla PC, Gupta M, Chan L, Al-Omran M, Teoh H, Verma S (2010) Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol 299(3):H656–H663. doi:10.1152/ajpheart.00115.2010 PubMedCentral CrossRef PubMed - 作者单位：Ling-Hsuan Wu (1)
Chingju Lin (2)
Hsiao-Yun Lin (3)
Yu-Shu Liu (4)
Caren Yu-Ju Wu (4)
Cheng-Fang Tsai (5)
Pei-Chun Chang (6)
Wei-Lan Yeh (7)
Dah-Yuu Lu (3) (8)
1. Department of Biological Science and Technology, College of Life Science, China Medial University, Taichung, Taiwan
2. Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan
3. Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan
4. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
5. Department of Biotechnology, Asia University, Taichung, Taiwan
6. Department of Bioinformatics, Asia University, Taichung, Taiwan
7. Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua, Taiwan
8. Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan - 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
- 出版者：Springer US
- ISSN：1559-1182
文摘
Accumulating evidence suggests that neuroinflammation is closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. The hallmark of neuroinflammation is considered to be microglial activation in the central nervous system (CNS). Activated microglia release pro-inflammatory cytokines which cause neuroinflammation and progressive neuronal cell death. Therefore, inhibition of microglial activation is considered an important strategy in the development of neuroprotective strategy. Naringenin, a flavonoid found in citrus fruits and tomatoes, has been reported to have anti-oxidant, anti-cancer, and anti-inflammatory properties. However, the mechanism of its beneficial anti-inflammatory effects in the CNS is poorly understood. In this study, we demonstrated that naringenin inhibites the release of nitric oxide (NO), the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), as well as pro-inflammatory cytokines in microglial cells. Treatment of naringenin also induced suppressors of cytokine signaling (SOCS)-3 expression in microglia. The SOCS-3 expression and anti-inflammatory effects of naringenin were found to be regulated by adenosine monophosphate-activated protein kinase α (AMPKα) and protein kinase C δ (PKCδ). Besides, naringenin exerted protective property against neurotoxicity caused by LPS-induced microglial activation. Our findings suggest that naringenin-inhibited iNOS and COX-2 expression is mediated by SOCS-3 activation through AMPKα and PKCδ signaling pathways. In a mouse model, naringenin also showed significant protective effects on microglial activation and improved motor coordination function as well. Therefore, naringenin that involves in anti-neuroinflammatory responses and neuroprotection might be a potential agent for treatment of inflammation-associated disorders. Keywords Neuroinflammation Microglia CNS Naringenin SOCS-3