Mechanisms of human lymphotoxin beta receptor activation on upregulation of CCL5/RANTES production

Diana Yu Wung Yeh, Chia Chang Wu, Yi Ping Chin, Chia Jung Lu, Yuan Hung Wang, Mei Chieh Chen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Human lymphotoxin-β receptor (LTβR), a member of the tumor necrosis factor receptor superfamily, plays an essential role in secondary lymphoid organ development, host defense, chemokine secretion, and apoptosis. In our study, LTβR activations by different stimulations were all found to induce RANTES secretion. Overexpression of LTβR or stimulation LTβR by ligands or agonistic antibody in human lung epithelial cells induced RANTES secretion However, the regulatory mechanism and the signaling cascade have not been fully elucidated. Therefore, the aim of this study was to elucidate the mechanism underlying LTβR-mediated RANTES production. Our study indicated that activation of JNK and ERK was important for the regulation of RANTES secretion. In addition, dominant negative mutants of ASK1, TAK1, and MEKK1 inhibited LTβR-induced RANTES expression. The dominant negative mutants of TRAF2, 3, and 5 also inhibited LTβR-mediated RANTES secretion. Chromatin immunoprecipitation analysis showed that LTβR activation induced the binding of c-Jun and NF-κB to the RANTES promoter. The results of this study show that LTβR activates ASK1, TAK1, and MEKK1 cascades via TRAF2, 3, and 5, resulting in the activation of JNK and ERK, which promotes the binding of c-Jun and NF-κB to the RANTES promoter, thereby increasing RANTES expression and secretion.

Original languageEnglish
Pages (from-to)220-229
Number of pages10
JournalInternational Immunopharmacology
Volume28
Issue number1
DOIs
Publication statusPublished - Jun 22 2015

Fingerprint

Lymphotoxin beta Receptor
Lymphotoxin-alpha
Chemokine CCL5
Up-Regulation
TNF Receptor-Associated Factor 2
human LTB protein
Tumor Necrosis Factor Receptors
Chromatin Immunoprecipitation
Chemokines
Epithelial Cells

Keywords

  • c-Jun
  • LTβR
  • MAPK
  • NF-κB
  • RANTES
  • TRAF

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Mechanisms of human lymphotoxin beta receptor activation on upregulation of CCL5/RANTES production. / Yeh, Diana Yu Wung; Wu, Chia Chang; Chin, Yi Ping; Lu, Chia Jung; Wang, Yuan Hung; Chen, Mei Chieh.

In: International Immunopharmacology, Vol. 28, No. 1, 22.06.2015, p. 220-229.

Research output: Contribution to journalArticle

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