Japanese encephalitis virus induces matrix metalloproteinase-9 in rat brain astrocytes via NF-ΚB signalling dependent on MAPKs and reactive oxygen species

Wei Hsuan Tung, Hsin Wen Tsai, I. Ta Lee, Hsi Lung Hsieh, Wei June Chen, Yuh Lien Chen, Chuen Mao Yang

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE Japanese encephalitis virus (JEV) is a member of the family Flaviviridae and JEV infection is a major cause of acute encephalopathy in children, which destroys cells in the CNS, including astrocytes and neurons. However, the detailed mechanisms underlying the inflammatory action of JEV are largely unclear. EXPERIMENTAL APPROACH The effect of JEV on the expression of matrix metalloproteinase (MMP)-9 was determined by gelatin zymography, Western blot analysis, real-time PCR and promoter assay. The involvement of the NADPH oxidase and reactive oxygen species (ROS), MAPKs, and the transcription factor NF-ΚB in these responses was investigated by using selective pharmacological inhibitors and transfection with appropriate siRNAs. KEY RESULTS JEV induced the expression of the pro-form of MMP-9 in rat brain astrocytes (RBA-1 cells). In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47 phox, ERK1, JNK2 and p38. In addition, JEV-induced MMP-9 expression was reduced by pretreatment with an inhibitor of NF-ΚB (helenalin) or transfection with p65 siRNA. Moreover, JEV-stimulated NF-ΚB activation was inhibited by pretreatment with the inhibitors of NADPH oxidase and MAPKs. CONCLUSIONS AND IMPLICATIONS MMP-9 expression induced by JEV infection of RBA-1 cells was mediated through the generation of ROS and activation of p42/p44 MAPK, p38 MAPK and JNK1/2, leading to NF-ΚB activation.

Original languageEnglish
Pages (from-to)1566-1583
Number of pages18
JournalBritish Journal of Pharmacology
Volume161
Issue number7
DOIs
Publication statusPublished - Dec 1 2010
Externally publishedYes

Fingerprint

Japanese Encephalitis Virus
Matrix Metalloproteinase 9
Astrocytes
Reactive Oxygen Species
Brain
NADPH Oxidase
Transfection
Flaviviridae
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Acetylcysteine
Brain Diseases
p38 Mitogen-Activated Protein Kinases
Gelatin
Infection
Small Interfering RNA
Chlorides
Real-Time Polymerase Chain Reaction

Keywords

  • Japanese encephalitis virus
  • MAPKs
  • Matrix metalloproteinase-9
  • NF-ΚB
  • ROS

ASJC Scopus subject areas

  • Pharmacology

Cite this

Japanese encephalitis virus induces matrix metalloproteinase-9 in rat brain astrocytes via NF-ΚB signalling dependent on MAPKs and reactive oxygen species. / Tung, Wei Hsuan; Tsai, Hsin Wen; Lee, I. Ta; Hsieh, Hsi Lung; Chen, Wei June; Chen, Yuh Lien; Yang, Chuen Mao.

In: British Journal of Pharmacology, Vol. 161, No. 7, 01.12.2010, p. 1566-1583.

Research output: Contribution to journalArticle

Tung, Wei Hsuan ; Tsai, Hsin Wen ; Lee, I. Ta ; Hsieh, Hsi Lung ; Chen, Wei June ; Chen, Yuh Lien ; Yang, Chuen Mao. / Japanese encephalitis virus induces matrix metalloproteinase-9 in rat brain astrocytes via NF-ΚB signalling dependent on MAPKs and reactive oxygen species. In: British Journal of Pharmacology. 2010 ; Vol. 161, No. 7. pp. 1566-1583.
@article{51d16b6874334bda8bff52b8e7fe8239,
title = "Japanese encephalitis virus induces matrix metalloproteinase-9 in rat brain astrocytes via NF-ΚB signalling dependent on MAPKs and reactive oxygen species",
abstract = "BACKGROUND AND PURPOSE Japanese encephalitis virus (JEV) is a member of the family Flaviviridae and JEV infection is a major cause of acute encephalopathy in children, which destroys cells in the CNS, including astrocytes and neurons. However, the detailed mechanisms underlying the inflammatory action of JEV are largely unclear. EXPERIMENTAL APPROACH The effect of JEV on the expression of matrix metalloproteinase (MMP)-9 was determined by gelatin zymography, Western blot analysis, real-time PCR and promoter assay. The involvement of the NADPH oxidase and reactive oxygen species (ROS), MAPKs, and the transcription factor NF-ΚB in these responses was investigated by using selective pharmacological inhibitors and transfection with appropriate siRNAs. KEY RESULTS JEV induced the expression of the pro-form of MMP-9 in rat brain astrocytes (RBA-1 cells). In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47 phox, ERK1, JNK2 and p38. In addition, JEV-induced MMP-9 expression was reduced by pretreatment with an inhibitor of NF-ΚB (helenalin) or transfection with p65 siRNA. Moreover, JEV-stimulated NF-ΚB activation was inhibited by pretreatment with the inhibitors of NADPH oxidase and MAPKs. CONCLUSIONS AND IMPLICATIONS MMP-9 expression induced by JEV infection of RBA-1 cells was mediated through the generation of ROS and activation of p42/p44 MAPK, p38 MAPK and JNK1/2, leading to NF-ΚB activation.",
keywords = "Japanese encephalitis virus, MAPKs, Matrix metalloproteinase-9, NF-ΚB, ROS",
author = "Tung, {Wei Hsuan} and Tsai, {Hsin Wen} and Lee, {I. Ta} and Hsieh, {Hsi Lung} and Chen, {Wei June} and Chen, {Yuh Lien} and Yang, {Chuen Mao}",
year = "2010",
month = "12",
day = "1",
doi = "10.1111/j.1476-5381.2010.00982.x",
language = "English",
volume = "161",
pages = "1566--1583",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

TY - JOUR

T1 - Japanese encephalitis virus induces matrix metalloproteinase-9 in rat brain astrocytes via NF-ΚB signalling dependent on MAPKs and reactive oxygen species

AU - Tung, Wei Hsuan

AU - Tsai, Hsin Wen

AU - Lee, I. Ta

AU - Hsieh, Hsi Lung

AU - Chen, Wei June

AU - Chen, Yuh Lien

AU - Yang, Chuen Mao

PY - 2010/12/1

Y1 - 2010/12/1

N2 - BACKGROUND AND PURPOSE Japanese encephalitis virus (JEV) is a member of the family Flaviviridae and JEV infection is a major cause of acute encephalopathy in children, which destroys cells in the CNS, including astrocytes and neurons. However, the detailed mechanisms underlying the inflammatory action of JEV are largely unclear. EXPERIMENTAL APPROACH The effect of JEV on the expression of matrix metalloproteinase (MMP)-9 was determined by gelatin zymography, Western blot analysis, real-time PCR and promoter assay. The involvement of the NADPH oxidase and reactive oxygen species (ROS), MAPKs, and the transcription factor NF-ΚB in these responses was investigated by using selective pharmacological inhibitors and transfection with appropriate siRNAs. KEY RESULTS JEV induced the expression of the pro-form of MMP-9 in rat brain astrocytes (RBA-1 cells). In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47 phox, ERK1, JNK2 and p38. In addition, JEV-induced MMP-9 expression was reduced by pretreatment with an inhibitor of NF-ΚB (helenalin) or transfection with p65 siRNA. Moreover, JEV-stimulated NF-ΚB activation was inhibited by pretreatment with the inhibitors of NADPH oxidase and MAPKs. CONCLUSIONS AND IMPLICATIONS MMP-9 expression induced by JEV infection of RBA-1 cells was mediated through the generation of ROS and activation of p42/p44 MAPK, p38 MAPK and JNK1/2, leading to NF-ΚB activation.

AB - BACKGROUND AND PURPOSE Japanese encephalitis virus (JEV) is a member of the family Flaviviridae and JEV infection is a major cause of acute encephalopathy in children, which destroys cells in the CNS, including astrocytes and neurons. However, the detailed mechanisms underlying the inflammatory action of JEV are largely unclear. EXPERIMENTAL APPROACH The effect of JEV on the expression of matrix metalloproteinase (MMP)-9 was determined by gelatin zymography, Western blot analysis, real-time PCR and promoter assay. The involvement of the NADPH oxidase and reactive oxygen species (ROS), MAPKs, and the transcription factor NF-ΚB in these responses was investigated by using selective pharmacological inhibitors and transfection with appropriate siRNAs. KEY RESULTS JEV induced the expression of the pro-form of MMP-9 in rat brain astrocytes (RBA-1 cells). In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47 phox, ERK1, JNK2 and p38. In addition, JEV-induced MMP-9 expression was reduced by pretreatment with an inhibitor of NF-ΚB (helenalin) or transfection with p65 siRNA. Moreover, JEV-stimulated NF-ΚB activation was inhibited by pretreatment with the inhibitors of NADPH oxidase and MAPKs. CONCLUSIONS AND IMPLICATIONS MMP-9 expression induced by JEV infection of RBA-1 cells was mediated through the generation of ROS and activation of p42/p44 MAPK, p38 MAPK and JNK1/2, leading to NF-ΚB activation.

KW - Japanese encephalitis virus

KW - MAPKs

KW - Matrix metalloproteinase-9

KW - NF-ΚB

KW - ROS

UR - http://www.scopus.com/inward/record.url?scp=78149371023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149371023&partnerID=8YFLogxK

U2 - 10.1111/j.1476-5381.2010.00982.x

DO - 10.1111/j.1476-5381.2010.00982.x

M3 - Article

VL - 161

SP - 1566

EP - 1583

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 7

ER -