Abstract

In this study, we investigated the role of ASK1 in PGN-induced C/EBPβ activation and COX-2 expression in RAW 264.7 macrophages. The PGN-induced COX-2 expression was attenuated by the DNs of ASK1, JNK1, JNK2, a JNK inhibitor (SP600125), and an AP-1 inhibitor (curcumin). PGN caused ASK1 dephosphorylation time-dependently at Ser967, dissociation from the ASK1-14-3-3 complex, and subsequent ASK1 activation. In addition, PGN activated PP2A and suppression of PP2A by okadaic acid markedly inhibited PGN-induced ASK1 Ser967 dephosphorylation and COX-2 expression. PGN induced the activation of the JNK-AP-1 signaling cascade downstream of ASK1. PGN-increased C/EBPβ expression and DNA-binding activity were inhibited by the ASK1-JNK-AP-1 signaling blockade. COX-2 promoter luciferase activity induced by PGN was attenuated in cells transfected with the COX-2 reporter construct possessing the C/EBP-binding site mutation. In addition, the ASK1-JNK-AP-1-C/EBPβ cascade was activated in human peripheral mononuclear cells exposure to PGN. The TLR2 agonist Pam3CSK4 was also shown to induce ASK1 Ser967 dephosphorylation, JNK and c-jun phosphorylation, C/EBPβ activation, and COX-2 expression in RAW 264.7 macrophages. PGN-induced COX-2 promoter luciferase activity was prevented by selective inhibition of TLR2 and c-Jun in RAW 264.7 macrophages. Our data demonstrate that PGN might activate the TLR2-mediated PP2A-ASK1-JNK-AP-1-C/EBPβ cascade and subsequent COX-2 expression in RAW 264.7 macrophages.

Original languageEnglish
Pages (from-to)1069-1082
Number of pages14
JournalJournal of Leukocyte Biology
Volume87
Issue number6
DOIs
Publication statusPublished - Jun 2010

Fingerprint

MAP Kinase Kinase Kinase 5
Peptidoglycan
Transcription Factor AP-1
Macrophages
Luciferases
Okadaic Acid
Curcumin
Binding Sites
Phosphorylation
Mutation
DNA

Keywords

  • Inflammation
  • Monocytes/ macrophages
  • Signal transduction
  • Toll-like receptor
  • Transcription factors

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Apoptosis signal-regulating kinase 1 in peptidoglycan-induced COX-2 expression in macrophages. / Hsu, Ming Jen; Chang, Chia Kai; Chen, Mei Chieh; Chen, Bing Chang; Ma, Hon Ping; Hong, Chuang Ye; Lin, Chien-Huang.

In: Journal of Leukocyte Biology, Vol. 87, No. 6, 06.2010, p. 1069-1082.

Research output: Contribution to journalArticle

@article{7d2f718bc70f4688ad737e520c65e042,
title = "Apoptosis signal-regulating kinase 1 in peptidoglycan-induced COX-2 expression in macrophages",
abstract = "In this study, we investigated the role of ASK1 in PGN-induced C/EBPβ activation and COX-2 expression in RAW 264.7 macrophages. The PGN-induced COX-2 expression was attenuated by the DNs of ASK1, JNK1, JNK2, a JNK inhibitor (SP600125), and an AP-1 inhibitor (curcumin). PGN caused ASK1 dephosphorylation time-dependently at Ser967, dissociation from the ASK1-14-3-3 complex, and subsequent ASK1 activation. In addition, PGN activated PP2A and suppression of PP2A by okadaic acid markedly inhibited PGN-induced ASK1 Ser967 dephosphorylation and COX-2 expression. PGN induced the activation of the JNK-AP-1 signaling cascade downstream of ASK1. PGN-increased C/EBPβ expression and DNA-binding activity were inhibited by the ASK1-JNK-AP-1 signaling blockade. COX-2 promoter luciferase activity induced by PGN was attenuated in cells transfected with the COX-2 reporter construct possessing the C/EBP-binding site mutation. In addition, the ASK1-JNK-AP-1-C/EBPβ cascade was activated in human peripheral mononuclear cells exposure to PGN. The TLR2 agonist Pam3CSK4 was also shown to induce ASK1 Ser967 dephosphorylation, JNK and c-jun phosphorylation, C/EBPβ activation, and COX-2 expression in RAW 264.7 macrophages. PGN-induced COX-2 promoter luciferase activity was prevented by selective inhibition of TLR2 and c-Jun in RAW 264.7 macrophages. Our data demonstrate that PGN might activate the TLR2-mediated PP2A-ASK1-JNK-AP-1-C/EBPβ cascade and subsequent COX-2 expression in RAW 264.7 macrophages.",
keywords = "Inflammation, Monocytes/ macrophages, Signal transduction, Toll-like receptor, Transcription factors",
author = "Hsu, {Ming Jen} and Chang, {Chia Kai} and Chen, {Mei Chieh} and Chen, {Bing Chang} and Ma, {Hon Ping} and Hong, {Chuang Ye} and Chien-Huang Lin",
year = "2010",
month = "6",
doi = "10.1189/jlb.1009668",
language = "English",
volume = "87",
pages = "1069--1082",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "6",

}

TY - JOUR

T1 - Apoptosis signal-regulating kinase 1 in peptidoglycan-induced COX-2 expression in macrophages

AU - Hsu, Ming Jen

AU - Chang, Chia Kai

AU - Chen, Mei Chieh

AU - Chen, Bing Chang

AU - Ma, Hon Ping

AU - Hong, Chuang Ye

AU - Lin, Chien-Huang

PY - 2010/6

Y1 - 2010/6

N2 - In this study, we investigated the role of ASK1 in PGN-induced C/EBPβ activation and COX-2 expression in RAW 264.7 macrophages. The PGN-induced COX-2 expression was attenuated by the DNs of ASK1, JNK1, JNK2, a JNK inhibitor (SP600125), and an AP-1 inhibitor (curcumin). PGN caused ASK1 dephosphorylation time-dependently at Ser967, dissociation from the ASK1-14-3-3 complex, and subsequent ASK1 activation. In addition, PGN activated PP2A and suppression of PP2A by okadaic acid markedly inhibited PGN-induced ASK1 Ser967 dephosphorylation and COX-2 expression. PGN induced the activation of the JNK-AP-1 signaling cascade downstream of ASK1. PGN-increased C/EBPβ expression and DNA-binding activity were inhibited by the ASK1-JNK-AP-1 signaling blockade. COX-2 promoter luciferase activity induced by PGN was attenuated in cells transfected with the COX-2 reporter construct possessing the C/EBP-binding site mutation. In addition, the ASK1-JNK-AP-1-C/EBPβ cascade was activated in human peripheral mononuclear cells exposure to PGN. The TLR2 agonist Pam3CSK4 was also shown to induce ASK1 Ser967 dephosphorylation, JNK and c-jun phosphorylation, C/EBPβ activation, and COX-2 expression in RAW 264.7 macrophages. PGN-induced COX-2 promoter luciferase activity was prevented by selective inhibition of TLR2 and c-Jun in RAW 264.7 macrophages. Our data demonstrate that PGN might activate the TLR2-mediated PP2A-ASK1-JNK-AP-1-C/EBPβ cascade and subsequent COX-2 expression in RAW 264.7 macrophages.

AB - In this study, we investigated the role of ASK1 in PGN-induced C/EBPβ activation and COX-2 expression in RAW 264.7 macrophages. The PGN-induced COX-2 expression was attenuated by the DNs of ASK1, JNK1, JNK2, a JNK inhibitor (SP600125), and an AP-1 inhibitor (curcumin). PGN caused ASK1 dephosphorylation time-dependently at Ser967, dissociation from the ASK1-14-3-3 complex, and subsequent ASK1 activation. In addition, PGN activated PP2A and suppression of PP2A by okadaic acid markedly inhibited PGN-induced ASK1 Ser967 dephosphorylation and COX-2 expression. PGN induced the activation of the JNK-AP-1 signaling cascade downstream of ASK1. PGN-increased C/EBPβ expression and DNA-binding activity were inhibited by the ASK1-JNK-AP-1 signaling blockade. COX-2 promoter luciferase activity induced by PGN was attenuated in cells transfected with the COX-2 reporter construct possessing the C/EBP-binding site mutation. In addition, the ASK1-JNK-AP-1-C/EBPβ cascade was activated in human peripheral mononuclear cells exposure to PGN. The TLR2 agonist Pam3CSK4 was also shown to induce ASK1 Ser967 dephosphorylation, JNK and c-jun phosphorylation, C/EBPβ activation, and COX-2 expression in RAW 264.7 macrophages. PGN-induced COX-2 promoter luciferase activity was prevented by selective inhibition of TLR2 and c-Jun in RAW 264.7 macrophages. Our data demonstrate that PGN might activate the TLR2-mediated PP2A-ASK1-JNK-AP-1-C/EBPβ cascade and subsequent COX-2 expression in RAW 264.7 macrophages.

KW - Inflammation

KW - Monocytes/ macrophages

KW - Signal transduction

KW - Toll-like receptor

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=77954021023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954021023&partnerID=8YFLogxK

U2 - 10.1189/jlb.1009668

DO - 10.1189/jlb.1009668

M3 - Article

C2 - 20200402

AN - SCOPUS:77954021023

VL - 87

SP - 1069

EP - 1082

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 6

ER -