Double-stranded RNA mediates interferon regulatory factor 3 activation and interleukin-6 production by engaging Toll-like receptor 3 in human brain astrocytes

Hyemi Kim, Eunjung Yang, Jeonggi Lee, Se Hoon Kim, Jeon Soo Shin, Joo Young Park, Sun Ju Choi, Se Jong Kim, In Hong Choi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Toll-like receptor 3 (TLR3) participates in the innate immune response by recognizing viral pathogens. In this study, human brain astrocytes were found to constitutively express TLR3, and this expression was increased by interferon-γ (IFN-γ) or double-stranded RNA (dsRNA). Treatment employing dsRNA in astrocytes induced IFN regulatory factor 3 (IRF3) phosphorylation, dimer formation and nuclear translocation followed by STAT1 activation. This treatment also activated nuclear factor-κB, p38 and c-Jun N-terminal kinase significantly, while activating extracellular signal-regulated kinase to a lesser extent. Treatment with anti-TLR3 antibody inhibited dsRNA-mediated interleukin-6 (IL-6) production. In the presence of mitogen-activated protein kinase inhibitors, astrocytes failed to secrete IL-6 in response to dsRNA treatment. Therefore, dsRNA-induced IL-6 production is dependent on mitogen-activated protein kinases and type I IFN production is dependent on IRF3 in brain astrocytes. These results suggest that brain inflammation, which produces inflammatory cytokines and type I IFNs, may enhance TLR3 expression in astrocytes. Additionally, upregulated TLR3 might modulate inflammatory processes by producing proinflammatory cytokines.

Original languageEnglish
Pages (from-to)480-488
Number of pages9
JournalImmunology
Volume124
Issue number4
DOIs
Publication statusPublished - 2008 Aug 1

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Interferon Regulatory Factor-3
Toll-Like Receptor 3
Double-Stranded RNA
Astrocytes
Interleukin-6
Brain
Mitogen-Activated Protein Kinases
Cytokines
JNK Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Encephalitis
Protein Kinase Inhibitors
Innate Immunity
Interferons
Phosphorylation
human TLR3 protein
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kim, Hyemi ; Yang, Eunjung ; Lee, Jeonggi ; Kim, Se Hoon ; Shin, Jeon Soo ; Park, Joo Young ; Choi, Sun Ju ; Kim, Se Jong ; Choi, In Hong. / Double-stranded RNA mediates interferon regulatory factor 3 activation and interleukin-6 production by engaging Toll-like receptor 3 in human brain astrocytes. In: Immunology. 2008 ; Vol. 124, No. 4. pp. 480-488.
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Double-stranded RNA mediates interferon regulatory factor 3 activation and interleukin-6 production by engaging Toll-like receptor 3 in human brain astrocytes. / Kim, Hyemi; Yang, Eunjung; Lee, Jeonggi; Kim, Se Hoon; Shin, Jeon Soo; Park, Joo Young; Choi, Sun Ju; Kim, Se Jong; Choi, In Hong.

In: Immunology, Vol. 124, No. 4, 01.08.2008, p. 480-488.

Research output: Contribution to journalArticle

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