TNFα and IL-1β are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS

Wenwen Zheng, Xuexing Zheng, Shue Liu, Hongsheng Ouyang, Roy C Levitt, Keith A Candiotti, Shuanglin Hao

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

A growing body of evidence recently suggests that glial cell activation plays an important role in several neurodegenerative diseases and neuropathic pain. Microglia in the central nervous system express toll-like receptor 4 (TLR4) that is traditionally accepted as the primary receptor of lipopolysaccharide (LPS). LPS activates TLR4 signaling pathways to induce the production of proinflammatory molecules. In the present studies, we verified the LPS signaling pathways using cultured highly aggressively proliferating immortalized (HAPI) microglial cells. We found that HAPI cells treated with LPS upregulated the expression of TLR4, phospho-JNK (pJNK) and phospho-NF-κB (pNF-κB), TNFα and IL-1β. Silencing TLR4 with siRNA reduced the expression of pJNK, TNFα and IL-1β, but not pNF-κB in the cells. Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the expression of TNFα and IL-1β. Unexpectedly, we found that inhibition of Nod1 with ML130 significantly reduced the expression of pNF-κB. Inhibition of NF-κB also reduced the expression of TNFα and IL-1β. Nod1 ligand, DAP induced the upregulation of pNF-κB which was blocked by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-dependent, and that pNF-κB is Nod1-dependent in HAPI cells treated with LPS. Either TLR4-JNK or Nod1-NF-κB pathways is involved in the expression of TNFα and IL-1β.

Original languageEnglish
Pages (from-to)762-767
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume420
Issue number4
DOIs
StatePublished - Apr 20 2012

Fingerprint

Toll-Like Receptor 4
Interleukin-1
Lipopolysaccharides
CD14 Antigens
Neurodegenerative diseases
Microglia
Neurology
Neuralgia
Neuroglia
Neurodegenerative Diseases
Small Interfering RNA
Up-Regulation
Central Nervous System
Chemical activation
Ligands
Molecules

Keywords

  • Cytokines
  • JNK
  • Microglia
  • NF-κB
  • Nod1
  • TLR4

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

TNFα and IL-1β are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS. / Zheng, Wenwen; Zheng, Xuexing; Liu, Shue; Ouyang, Hongsheng; Levitt, Roy C; Candiotti, Keith A; Hao, Shuanglin.

In: Biochemical and Biophysical Research Communications, Vol. 420, No. 4, 20.04.2012, p. 762-767.

Research output: Contribution to journalArticle

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