RGD Reference Report - JAK-STAT signaling mediates gangliosides-induced inflammatory responses in brain microglial cells. - Rat Genome Database

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JAK-STAT signaling mediates gangliosides-induced inflammatory responses in brain microglial cells.

Authors: Kim, OS  Park, EJ  Joe, EH  Jou, I 
Citation: Kim OS, etal., J Biol Chem 2002 Oct 25;277(43):40594-601. Epub 2002 Aug 20.
RGD ID: 1299060
Pubmed: PMID:12191995   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M203885200   (Journal Full-text)

Neuronal cell membranes are particularly rich in gangliosides, which play important roles in brain physiology and pathology. Previously, we reported that gangliosides could act as microglial activators and are thus likely to participate in many neuronal diseases. In the present study we provide evidence that JAK-STAT inflammatory signaling mediates gangliosides-stimulated microglial activation. Both in rat primary microglia and murine BV2 microglial cells, gangliosides stimulated nuclear factor binding to GAS/ISRE elements, which are known to be STAT-binding sites. Consistent with this, gangliosides rapidly activated JAK1 and JAK2 and induced phosphorylation of STAT1 and STAT3. In addition, gangliosides increased transcription of the inflammation-associated genes inducible nitric-oxide synthase, ICAM-1, and MCP-1, which are reported to contain STAT-binding elements in their promoter regions. AG490, a JAK inhibitor, reduced induction of these genes, nuclear factor binding activity, and activation of STAT1 and -3 in gangliosides-treated microglia. AG490 also inhibited gangliosides-induced release of nitric oxide, an inflammation hallmark. Furthermore, AG490 markedly reduced activation of ERK1/2 MAPK, indicating that ERKs act downstream of JAK-STAT signaling during microglial activation. However, AG490 did not affect activation of p38 MAPK. We also report that the sialic acid residues present on gangliosides may be one of the essential components in activation of JAK-STAT signaling. The present study indicates that JAK-STAT signaling is an early event in gangliosides-induced brain inflammatory responses.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell surface receptor signaling pathway via JAK-STAT  IMP 1299060 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Jak-Stat signaling pathway   IDA 1299060 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Stat1  (signal transducer and activator of transcription 1)

Objects referenced in this article
Gene Stat3 signal transducer and activator of transcription 3 Rattus norvegicus

Additional Information