Lymphotoxin β receptor induces interleukin 8 gene expression via NF-κB and AP-1 activation

Ying Hsin Chang, Shie Liang Hsieh, Mei Chieh Chen, Wan Wan Lin

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The human lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor (TNF) receptor superfamily, is essential for not only the development and organization of secondary lymphoid tissues, but also for chemokine release. Even though LTβR was shown to recruit TNF-receptor-associated factor (TRAF) 2, 3, and 5, and to induce cell apoptosis or NF-κB activation, however, the downstream signaling leading to chemokine expression is not illustrated yet. In this study, we find that overexpression of LTβR in HEK293 cells increases IL-8 promoter activity and leads to IL-8 release. LTβR-induced IL-8 gene expression requires NF-κB (-80 to -71) and AP-1 (-126 to -12) binding sites located in IL-8 promoter, and NF-κB is more crucial than AP-1 for IL-8 gene expression. Reporter assay with dominant-negative mutants of TRAFs reveals that TRAF2, 3, and 5, as well as the downstream signal molecules NIK, IKKα, and IKKβ, are involved in IL-8 gene expression. LTβR-mediated IL-8 response was inhibited by the dominant-negative mutants of ASK1, MKK4, MKK7, and JNK, but not by those of MEKK1, TAK1, MEK, ERK, and p38 MAPK. This suggests that IL-8 induction by LTβR is via TRAFs-elicited signaling pathways, including NIK/IKK-dependent NF-κB activation and ASK/MKK/JNK-dependent AP-1 activation.

Original languageEnglish
Pages (from-to)166-174
Number of pages9
JournalExperimental Cell Research
Volume278
Issue number2
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Interleukin-8 Receptors
Lymphotoxin-alpha
Transcription Factor AP-1
Interleukin-8
Gene Expression
Chemokine CCL21
TNF Receptor-Associated Factor 2
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Tumor Necrosis Factor Receptors
HEK293 Cells
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Chemokines
Binding Sites
Apoptosis

Keywords

  • AP-1
  • ASK
  • IL-8
  • LTβR
  • NF-κB
  • TRAF

ASJC Scopus subject areas

  • Cell Biology

Cite this

Lymphotoxin β receptor induces interleukin 8 gene expression via NF-κB and AP-1 activation. / Chang, Ying Hsin; Hsieh, Shie Liang; Chen, Mei Chieh; Lin, Wan Wan.

In: Experimental Cell Research, Vol. 278, No. 2, 2002, p. 166-174.

Research output: Contribution to journalArticle

Chang, Ying Hsin ; Hsieh, Shie Liang ; Chen, Mei Chieh ; Lin, Wan Wan. / Lymphotoxin β receptor induces interleukin 8 gene expression via NF-κB and AP-1 activation. In: Experimental Cell Research. 2002 ; Vol. 278, No. 2. pp. 166-174.
@article{6045052a39c34c9ab2a962f9a55df8bd,
title = "Lymphotoxin β receptor induces interleukin 8 gene expression via NF-κB and AP-1 activation",
abstract = "The human lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor (TNF) receptor superfamily, is essential for not only the development and organization of secondary lymphoid tissues, but also for chemokine release. Even though LTβR was shown to recruit TNF-receptor-associated factor (TRAF) 2, 3, and 5, and to induce cell apoptosis or NF-κB activation, however, the downstream signaling leading to chemokine expression is not illustrated yet. In this study, we find that overexpression of LTβR in HEK293 cells increases IL-8 promoter activity and leads to IL-8 release. LTβR-induced IL-8 gene expression requires NF-κB (-80 to -71) and AP-1 (-126 to -12) binding sites located in IL-8 promoter, and NF-κB is more crucial than AP-1 for IL-8 gene expression. Reporter assay with dominant-negative mutants of TRAFs reveals that TRAF2, 3, and 5, as well as the downstream signal molecules NIK, IKKα, and IKKβ, are involved in IL-8 gene expression. LTβR-mediated IL-8 response was inhibited by the dominant-negative mutants of ASK1, MKK4, MKK7, and JNK, but not by those of MEKK1, TAK1, MEK, ERK, and p38 MAPK. This suggests that IL-8 induction by LTβR is via TRAFs-elicited signaling pathways, including NIK/IKK-dependent NF-κB activation and ASK/MKK/JNK-dependent AP-1 activation.",
keywords = "AP-1, ASK, IL-8, LTβR, NF-κB, TRAF",
author = "Chang, {Ying Hsin} and Hsieh, {Shie Liang} and Chen, {Mei Chieh} and Lin, {Wan Wan}",
year = "2002",
doi = "10.1006/excr.2002.5573",
language = "English",
volume = "278",
pages = "166--174",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Lymphotoxin β receptor induces interleukin 8 gene expression via NF-κB and AP-1 activation

AU - Chang, Ying Hsin

AU - Hsieh, Shie Liang

AU - Chen, Mei Chieh

AU - Lin, Wan Wan

PY - 2002

Y1 - 2002

N2 - The human lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor (TNF) receptor superfamily, is essential for not only the development and organization of secondary lymphoid tissues, but also for chemokine release. Even though LTβR was shown to recruit TNF-receptor-associated factor (TRAF) 2, 3, and 5, and to induce cell apoptosis or NF-κB activation, however, the downstream signaling leading to chemokine expression is not illustrated yet. In this study, we find that overexpression of LTβR in HEK293 cells increases IL-8 promoter activity and leads to IL-8 release. LTβR-induced IL-8 gene expression requires NF-κB (-80 to -71) and AP-1 (-126 to -12) binding sites located in IL-8 promoter, and NF-κB is more crucial than AP-1 for IL-8 gene expression. Reporter assay with dominant-negative mutants of TRAFs reveals that TRAF2, 3, and 5, as well as the downstream signal molecules NIK, IKKα, and IKKβ, are involved in IL-8 gene expression. LTβR-mediated IL-8 response was inhibited by the dominant-negative mutants of ASK1, MKK4, MKK7, and JNK, but not by those of MEKK1, TAK1, MEK, ERK, and p38 MAPK. This suggests that IL-8 induction by LTβR is via TRAFs-elicited signaling pathways, including NIK/IKK-dependent NF-κB activation and ASK/MKK/JNK-dependent AP-1 activation.

AB - The human lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor (TNF) receptor superfamily, is essential for not only the development and organization of secondary lymphoid tissues, but also for chemokine release. Even though LTβR was shown to recruit TNF-receptor-associated factor (TRAF) 2, 3, and 5, and to induce cell apoptosis or NF-κB activation, however, the downstream signaling leading to chemokine expression is not illustrated yet. In this study, we find that overexpression of LTβR in HEK293 cells increases IL-8 promoter activity and leads to IL-8 release. LTβR-induced IL-8 gene expression requires NF-κB (-80 to -71) and AP-1 (-126 to -12) binding sites located in IL-8 promoter, and NF-κB is more crucial than AP-1 for IL-8 gene expression. Reporter assay with dominant-negative mutants of TRAFs reveals that TRAF2, 3, and 5, as well as the downstream signal molecules NIK, IKKα, and IKKβ, are involved in IL-8 gene expression. LTβR-mediated IL-8 response was inhibited by the dominant-negative mutants of ASK1, MKK4, MKK7, and JNK, but not by those of MEKK1, TAK1, MEK, ERK, and p38 MAPK. This suggests that IL-8 induction by LTβR is via TRAFs-elicited signaling pathways, including NIK/IKK-dependent NF-κB activation and ASK/MKK/JNK-dependent AP-1 activation.

KW - AP-1

KW - ASK

KW - IL-8

KW - LTβR

KW - NF-κB

KW - TRAF

UR - http://www.scopus.com/inward/record.url?scp=0036038231&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036038231&partnerID=8YFLogxK

U2 - 10.1006/excr.2002.5573

DO - 10.1006/excr.2002.5573

M3 - Article

C2 - 12169272

AN - SCOPUS:0036038231

VL - 278

SP - 166

EP - 174

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 2

ER -