RGD Reference Report - TNFalpha and IL-1beta are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS. - Rat Genome Database

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TNFalpha and IL-1beta are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS.

Authors: Zheng, W  Zheng, X  Liu, S  Ouyang, H  Levitt, RC  Candiotti, KA  Hao, S 
Citation: Zheng W, etal., Biochem Biophys Res Commun. 2012 Apr 20;420(4):762-7. doi: 10.1016/j.bbrc.2012.03.068. Epub 2012 Mar 17.
RGD ID: 9831170
Pubmed: PMID:22450316   (View Abstract at PubMed)
PMCID: PMC5723156   (View Article at PubMed Central)
DOI: DOI:10.1016/j.bbrc.2012.03.068   (Journal Full-text)

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-kappaB (pNF-kappaB), TNFalpha and IL-1beta. Silencing TLR4 with siRNA reduced the expression of pJNK, TNFalpha and IL-1beta, but not pNF-kappaB in the cells. Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the expression of TNFalpha and IL-1beta. Unexpectedly, we found that inhibition of Nod1 with ML130 significantly reduced the expression of pNF-kappaB. Inhibition of NF-kappaB also reduced the expression of TNFalpha and IL-1beta. Nod1 ligand, DAP induced the upregulation of pNF-kappaB which was blocked by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-dependent, and that pNF-kappaB is Nod1-dependent in HAPI cells treated with LPS. Either TLR4-JNK or Nod1-NF-kappaB pathways is involved in the expression of TNFalpha and IL-1beta.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nod1Ratpositive regulation of interleukin-1 beta production  IMP  RGD 
Nod1Ratpositive regulation of tumor necrosis factor production  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nod1  (nucleotide-binding oligomerization domain containing 1)


Additional Information