Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Research

NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes

Authors: Hsi-Lung Hsieh, Chih-Chung Lin, Ruey-Horng Shih, Li-Der Hsiao, Chuen-Mao Yang

Published in: Journal of Neuroinflammation | Issue 1/2012

Login to get access

Abstract

Background

Lipoteichoic acid (LTA) is a component of gram-positive bacterial cell walls and may be elevated in the cerebrospinal fluid of patients suffering from meningitis. Among matrix metalloproteinases (MMPs), MMP-9 has been observed in patients with brain inflammatory diseases and may contribute to the pathology of brain diseases. Moreover, several studies have suggested that increased oxidative stress is implicated in the pathogenesis of brain inflammation and injury. However, the molecular mechanisms underlying LTA-induced redox signal and MMP-9 expression in brain astrocytes remain unclear.

Objective

Herein we explored whether LTA-induced MMP-9 expression was mediated through redox signals in rat brain astrocytes (RBA-1 cells).

Methods

Upregulation of MMP-9 by LTA was evaluated by zymographic and RT-PCR analyses. Next, the MMP-9 regulatory pathways were investigated by pretreatment with pharmacological inhibitors or transfection with small interfering RNAs (siRNAs), Western blotting, and chromatin immunoprecipitation (ChIP)-PCR and promoter activity reporter assays. Moreover, we determined the cell functional changes by migration assay.

Results

These results showed that LTA induced MMP-9 expression via a PKC(α)-dependent pathway. We further demonstrated that PKCα stimulated p47phox/NADPH oxidase 2 (Nox2)-dependent reactive oxygen species (ROS) generation and then activated the ATF2/AP-1 signals. The activated-ATF2 bound to the AP-1-binding site of MMP-9 promoter, and thereby turned on MMP-9 gene transcription. Additionally, the co-activator p300 also contributed to these responses. Functionally, LTA-induced MMP-9 expression enhanced astrocytic migration.

Conclusion

These results demonstrated that in RBA-1 cells, activation of ATF2/AP-1 by the PKC(α)-mediated Nox(2)/ROS signals is essential for upregulation of MMP-9 and cell migration enhanced by LTA.
Literature
1.
Aoki T, Sumii T, Mori T, Wang X, Lo EH: Blood–brain barrier disruption and matrix metalloproteinase-9 expression during reperfusion injury: mechanical versus embolic focal ischemia in spontaneously hypertensive rats. Stroke 2002, 33:2711–2717.CrossRefPubMed
2.
Harris JE, Nuttall RK, Elkington PT, Green JA, Horncastle DE, Graeber MB, Edwards DR, Friedland JS: Monocyte-astrocyte networks regulate matrix metalloproteinase gene expression and secretion in central nervous system tuberculosis in vitro and in vivo. J Immunol 2007, 178:1199–1207.CrossRefPubMed
3.
4.
Wu CY, Hsieh HL, Jou MJ, Yang CM: Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor-κB in interleukin-1β-induced matrix metalloproteinase-9 expression in rat brain astrocytes. J Neurochem 2004, 90:1477–1488.CrossRefPubMed
5.
Woo CH, Lim JH, Kim JH: Lipopolysaccharide induces matrix metalloproteinase-9 expression via a mitochondrial reactive oxygen species-p38 kinase-activator protein-1 pathway in Raw 264.7 cells. J Immunol 2004, 173:6973–6980.CrossRefPubMed
6.
Hsieh HL, Wang HH, Wu WB, Chu PJ, Yang CM: Transforming growth factor-β1 induces matrix metalloproteinase-9 and cell migration in astrocytes: roles of ROS-dependent ERK- and JNK-NF-κB pathways. J Neuroinflammation 2010, 7:88.CrossRefPubMedPubMedCentral
7.
Lee SJ, Lee S: Toll-like receptors and inflammation in the CNS. Curr Drug Targets Inflamm Allergy 2002, 1:181–191.CrossRefPubMed
8.
9.
Kinsner A, Pilotto V, Deininger S, Brown GC, Coecke S, Hartung T, Bal-Price A: Inflammatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrosative and oxidative stress, and caspase activation. J Neurochem 2005, 95:1132–1143.CrossRefPubMed
10.
Lehnardt S, Henneke P, Lien E, Kasper DL, Volpe JJ, Bechmann I, Nitsch R, Weber JR, Golenbock DT, Vartanian T: A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2/MyD88 pathway in microglia. J Immunol 2006, 177:583–592.CrossRefPubMed
11.
Neher JJ, Brown GC: Neurodegeneration in models of Gram-positive bacterial infections of the central nervous system. Biochem Soc Trans 2007, 35:1166–1167.CrossRefPubMed
12.
Carpentier PA, Duncan DS, Miller SD: Glial toll-like receptor signaling in central nervous system infection and autoimmunity. Brain Behav Immun 2008, 22:140–147.CrossRefPubMed
13.
Bowman CC, Rasley A, Tranguch SL, Marriott I: Cultured astrocytes express toll-like receptors for bacterial products. Glia 2003, 43:281–291.CrossRefPubMed
14.
Jack CS, Arbour N, Manusow J, Montgrain V, Blain M, McCrea E, Shapiro A, Antel JP: TLR signaling tailors innate immune responses in human microglia and astrocytes. J Immunol 2005, 175:4320–4330.CrossRefPubMed
15.
De Keyser J, Mostert JP, Koch MW: Dysfunctional astrocytes as key players in the pathogenesis of central nervous system disorders. J Neurol Sci 2008, 267:3–16.CrossRefPubMed
16.
Mullaly SC, Kubes P: The role of TLR2 in vivo following challenge with Staphylococcus aureus and prototypic ligands. J Immunol 2006, 177:8154–8163.CrossRefPubMed
17.
Hsieh HL, Wu CY, Yang CM: Bradykinin induces matrix metalloproteinase-9 expression and cell migration through a PKC-δ-dependent ERK/Elk-1 pathway in astrocytes. Glia 2008, 56:619–632.CrossRefPubMed
18.
Wang HH, Hsieh HL, Wu CY, Sun CC, Yang CM: Oxidized low-density lipoprotein induces matrix metalloproteinase-9 expression via a p42/p44 and JNK-dependent AP-1 pathway in brain astrocytes. Glia 2009, 57:24–38.CrossRefPubMed
19.
O’Neill LA: Primer: Toll-like receptor signaling pathways–what do rheumatologists need to know? Nat Clin Pract Rheumatol 2008, 4:319–327.CrossRefPubMed
20.
Souza LF, Jardim FR, Sauter IP, Souza MM, Barreto F, Margis R, Bernard EA: Lipoteichoic acid from Staphylococcus aureus increases matrix metalloproteinase 9 expression in RAW 264.7 macrophages: modulation by A2A and A2B adenosine receptors. Mol Immunol 2009, 46:937–942.CrossRefPubMed
21.
22.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007, 39:44–84.CrossRefPubMed
23.
Demchenko IT, Oury TD, Crapo JD, Piantadosi CA: Regulation of the brain’s vascular responses to oxygen. Circ Res 2002, 91:1031–1037.CrossRefPubMed
24.
Halliwell B: Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006, 97:1634–1658.CrossRefPubMed
25.
26.
Lee IT, Wang SW, Lee CW, Chang CC, Lin CC, Luo SF, Yang CM: Lipoteichoic acid induces HO-1 expression via the TLR2/MyD88/c-Src/NADPH oxidase pathway and Nrf2 in human tracheal smooth muscle cells. J Immunol 2008, 181:5098–5110.CrossRefPubMed
27.
Chatterjee PK, Zacharowski K, Cuzzocrea S, Brown PA, Stewart KN, Mota-Filipe H, Thiemermann C: Lipoteichoic acid from Staphylococcus aureus reduces renal ischemia/reperfusion injury. Kidney Int 2002, 62:1249–1263.CrossRefPubMed
28.
Jou TC, Jou MJ, Chen JY, Lee SY: Properties of rat brain astrocytes in long-term culture. J Formos Med Assoc 1985, 84:865–881.
29.
Hsieh HL, Yen MH, Jou MJ, Yang CM: Intracellular signalings underlying bradykinin-induced matrix metalloproteinase-9 expression in rat brain astrocyte-1. Cell Signal 2004, 16:1163–1176.CrossRefPubMed
30.
Reinehr R, Görg B, Becker S, Qvartskhava N, Bidmon HJ, Selbach O, Haas HL, Schliess F, Häussinger D: Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Glia 2007, 55:758–771.CrossRefPubMed
31.
LeBel CP, Ischiropoulos H, Bondy SC: Evaluation of the probe 2′,7′-dichlorofluorescein as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 1992, 5:227–231.CrossRefPubMed
32.
Parinandi NL, Kleinberg MA, Usatyuk PV, Cummings RJ, Pennathur A, Cardounel AJ, Zweier JL, Garcia JG, Natarajan V: Hyperoxia-induced NAD(P)H oxidase activation and regulation by MAP kinases in human lung endothelial cells. Am J Physiol Lung Cell Mol Physiol 2003, 284:L26-L38.CrossRefPubMed
33.
Nelson KK, Melendez JA: Mitochondrial redox control of matrix metalloproteinases. Free Radic Biol Med 2004, 37:768–784.CrossRefPubMed
34.
Infanger DW, Sharma RV, Davisson RL: NADPH oxidases of the brain: distribution, regulation, and function. Antioxid Redox Signal 2006, 8:1583–1596.CrossRefPubMed
35.
Bedard K, Krause KH: The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007, 87:245–313.CrossRefPubMed
36.
Fontayne A, Dang PM, Gougerot-Pocidalo MA, El-Benna J: Phosphorylation of p47phox sites by PKC α, βII, δ, and ζ: effect on binding to p22phox and on NADPH oxidase activation. Biochemistry 2002, 41:7743–7750.CrossRefPubMed
37.
Lin CW, Shen SC, Chien CC, Yang LY, Shia LT, Chen YC: 12-O-tetradecanoylphorbol-13-acetate-induced invasion/migration of glioblastoma cells through activating PKCα/ERK/NF-κB-dependent MMP-9 expression. J Cell Physiol 2010, 225:472–481.CrossRefPubMed
38.
Hsieh HL, Wang HH, Wu CY, Yang CM: Reactive Oxygen Species-Dependent c-Fos/Activator Protein 1 Induction Upregulates Heme Oxygenase-1 Expression by Bradykinin in Brain Astrocytes. Antioxid Redox Signal 2010, 13:1829–1844.CrossRefPubMed
39.
Chan HM, La Thangue NB: p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci 2001, 114:2363–2373.PubMed
40.
Svedin P, Hagberg H, Savman K, Zhu C, Mallard C: Matrix metalloproteinase-9 gene knock-out protects the immature brain after cerebral hypoxia-ischemia. J Neurosci 2007, 27:1511–1518.CrossRefPubMed
41.
McColl BW, Rothwell NJ, Allan SM: Systemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice. J Neurosci 2008, 28:9451–9462.CrossRefPubMed
42.
43.
Floyd RA: Neuroinflammatory processes are important in neurodegenerative diseases: an hypothesis to explain the increased formation of reactive oxygen and nitrogen species as major factors involved in neurodegenerative disease development. Free Radic Biol Med 1999, 26:1346–1355.CrossRefPubMed
44.
Qin L, Liu Y, Wang T, Wei SJ, Block ML, Wilson B, Liu B, Hong JS: NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem 2004, 279:1415–1421.CrossRefPubMed
45.
Abramov AY, Jacobson J, Wientjes F, Hothersall J, Canevari L, Duchen MR: Expression and modulation of an NADPH oxidase in mammalian astrocytes. J Neurosci 2005, 25:9176–9184.CrossRefPubMed
46.
Liu Q, Kang JH, Zheng RL: NADPH oxidase produces reactive oxygen species and maintains survival of rat astrocytes. Cell Biochem Funct 2005, 23:93–100.CrossRefPubMed
47.
Kim SY, Lee JG, Cho WS, Cho KH, Sakong J, Kim JR, Chin BR, Baek SH: Role of NADPH oxidase-2 in lipopolysaccharide-induced matrix metalloproteinase expression and cell migration. Immunol Cell Biol 2010, 88:197–204.CrossRefPubMed
48.
Sen CK, Packer L: Antioxidant and redox regulation of gene transcription. FASEB J 1996, 10:709–720.PubMed
49.
van Dam H, Castellazzi M: Distinct roles of Jun: Fos and Jun: ATF dimers in oncogenesis. Oncogene 2001, 20:2453–2464.CrossRefPubMed
50.
Kim ES, Sohn YW, Moon A: TGF-β-induced transcriptional activation of MMP-2 is mediated by activating transcription factor (ATF)2 in human breast epithelial cells. Cancer Lett 2007, 252:147–156.CrossRefPubMed
51.
Aggeli IK, Gaitanaki C, Beis I: Involvement of JNKs and p38-MAPK/MSK1 pathways in H2O2-induced upregulation of heme oxygenase-1 mRNA in H9c2 cells. Cell Signal 2006, 18:1801–1812.CrossRefPubMed
52.
Wu CY, Hsieh HL, Sun CC, Tseng CP, Yang CM: IL-1β induces proMMP-9 expression via c-Src-dependent PDGFR/PI3K/Akt/p300 cascade in rat brain astrocytes. J Neurochem 2008, 105:1499–1512.CrossRefPubMed
53.
Cheng SE, Lin CC, Lee IT, Hsu CK, Kou YR, Yang CM: Cigarette smoke extract regulates cytosolic phospholipase A2 expression via NADPH oxidase/MAPKs/AP-1 and p300 in human tracheal smooth muscle cells. J Cell Biochem 2011, 112:589–599.CrossRefPubMed
54.
Lauffenburger DA, Horwitz AF: Cell migration: a physically integrated molecular process. Cell 1996, 84:359–369.CrossRefPubMed
55.
Hsieh HL, Wang HH, Wu CY, Tung WH, Yang CM: Lipoteichoic acid induces matrix metalloproteinase-9 expression via transactivation of PDGF receptors and NF-κB activation in rat brain astrocytes. Neurotox Res 2010, 17:344–359.CrossRefPubMed
56.
Wang HH, Hsieh HL, Yang CM: Calmodulin kinase II-dependent transactivation of PDGF receptors mediates astrocytic MMP-9 expression and cell motility induced by lipoteichoic acid. J Neuroinflammation 2010, 7:84.CrossRefPubMedPubMedCentral
Metadata
Title
NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes
Authors
Hsi-Lung Hsieh
Chih-Chung Lin
Ruey-Horng Shih
Li-Der Hsiao
Chuen-Mao Yang
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-110

Other articles of this Issue 1/2012

Journal of Neuroinflammation 1/2012 Go to the issue

Research

Etiology of autistic features: the persisting neurotoxic effects of propionic acid

Research

Neuronal c-Abl activation leads to induction of cell cycle and interferon signaling pathways

Research

Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

Erratum

Erratum to: Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype

Research

Platelet-derived growth factor (PDGF)-BB-mediated induction of monocyte chemoattractant protein 1 in human astrocytes: implications for HIV-associated neuroinflammation

Research

α7 nicotinic acetylcholine receptor-mediated neuroprotection against dopaminergic neuron loss in an MPTP mouse model via inhibition of astrocyte activation