RGD Reference Report - A molecular platform in neurons regulates inflammation after spinal cord injury. - Rat Genome Database

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A molecular platform in neurons regulates inflammation after spinal cord injury.

Authors: De Rivero Vaccari, JP  Lotocki, G  Marcillo, AE  Dietrich, WD  Keane, RW 
Citation: de Rivero Vaccari JP, etal., J Neurosci. 2008 Mar 26;28(13):3404-14.
RGD ID: 2315889
Pubmed: PMID:18367607   (View Abstract at PubMed)
PMCID: PMC6670583   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.0157-08.2008   (Journal Full-text)

Vigorous immune responses are induced in the immune privileged CNS by injury and disease, but the molecular mechanisms regulating innate immunity in the CNS are poorly defined. The inflammatory response initiated by spinal cord injury (SCI) involves activation of interleukin-1beta (IL-1beta) that contributes to secondary cell death. In the peripheral immune response, the inflammasome activates caspase-1 to process proinflammatory cytokines, but the regulation of trauma-induced inflammation in the CNS is not clearly understood. Here we show that a molecular platform [NALP1 (NAcht leucine-rich-repeat protein 1) inflammasome] consisting of caspase-1, caspase-11, ASC (apoptosis-associated speck-like protein containing a caspase-activating recruitment domain), and NALP1 is expressed in neurons of the normal rat spinal cord and forms a protein assembly with the X-linked inhibitor of apoptosis protein (XIAP). Moderate cervical contusive SCI induced processing of IL-1beta, IL-18, activation of caspase-1, cleavage of XIAP, and promoted assembly of the multiprotein complex. Anti-ASC neutralizing antibodies administered to injured rats entered spinal cord neurons via a mechanism that was sensitive to carbenoxolone. Therapeutic neutralization of ASC reduced caspase-1 activation, XIAP cleavage, and interleukin processing, resulting in significant tissue sparing and functional improvement. Thus, rat spinal cord neurons contain a caspase-1, pro-ILbeta, and pro-IL-18 activating complex different from the human NALP1 inflammasome that constitutes an important arm of the innate CNS inflammatory response after SCI.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Spinal Cord Injuries  ISOCasp1 (Rattus norvegicus)2315889; 2315889protein:increased expression and increased activation:spinal cordRGD 
Spinal Cord Injuries  IDA 2315889protein:increased expression and increased activation:spinal cordRGD 
Spinal Cord Injuries  ISOIl18 (Rattus norvegicus)2315889; 2315889 RGD 
Spinal Cord Injuries  IDA 2315889 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protease binding  IPICasp1 (Rattus norvegicus)2315889 RGD 
protein binding  IPIPycard (Rattus norvegicus)2315889 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casp1  (caspase 1)
Il18  (interleukin 18)
Pycard  (PYD and CARD domain containing)

Genes (Mus musculus)
Casp1  (caspase 1)
Il18  (interleukin 18)

Genes (Homo sapiens)
CASP1  (caspase 1)
IL18  (interleukin 18)


Additional Information