RGD Reference Report - Macrophage inflammatory protein-3alpha plays a key role in the inflammatory cascade in rat focal cerebral ischemia. - Rat Genome Database

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Macrophage inflammatory protein-3alpha plays a key role in the inflammatory cascade in rat focal cerebral ischemia.

Authors: Terao, Y  Ohta, H  Oda, A  Nakagaito, Y  Kiyota, Y  Shintani, Y 
Citation: Terao Y, etal., Neurosci Res. 2009 May;64(1):75-82. doi: 10.1016/j.neures.2009.01.017. Epub 2009 Feb 13.
RGD ID: 7488896
Pubmed: PMID:19428685   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neures.2009.01.017   (Journal Full-text)

Although hypothermia is one of the most robust neuroprotectants clinically available, its underlying mechanisms remain unclear. Through microarray gene expression analysis, we previously identified several key molecules potentially involved in the efficacy of hypothermia in a 2h middle cerebral artery occlusion (MCAO) rat model, including cytokine and chemokine genes. The present study demonstrated that the expressions of 2 genes, macrophage inflammatory protein-3alpha (MIP-3alpha) and its receptor, CC-chemokine receptor 6 (CCR6), were upregulated in the model and were suppressed by hypothermia. To investigate the role of cerebral MIP-3alpha, it was administered into the rat striatum; dose- and time-dependent induction of CCR6 gene expression was observed. Interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha injection also induced sequential expressions of MIP-3alpha and CCR6. MIP-3alpha was found to be produced by proinflammatory cytokines in rat astrocytes, while it was suppressed by hypothermia. In turn, MIP-3alpha stimulated IL-1beta and inducible nitric oxide synthase expressions in rat microglia and rat brains. Furthermore, intracerebroventricular administration of an anti-rat MIP-3alpha-neutralizing antibody significantly reduced the infarct in MCAO rat brains. These findings suggest that MIP-3alpha plays a pivotal role in inflammatory cascades in ischemic brains, and may be a novel therapeutic target for cerebral ischemia.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCL20Humantransient cerebral ischemia treatmentISOCcl20 (Rattus norvegicus) RGD 
CCR6Humantransient cerebral ischemia  ISOCcr6 (Rattus norvegicus)mRNA:increased expression:brainRGD 
Ccl20Rattransient cerebral ischemia treatmentIMP  RGD 
Ccl20Mousetransient cerebral ischemia treatmentISOCcl20 (Rattus norvegicus) RGD 
Ccr6Rattransient cerebral ischemia  IEP mRNA:increased expression:brainRGD 
Ccr6Mousetransient cerebral ischemia  ISOCcr6 (Rattus norvegicus)mRNA:increased expression:brainRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ccl20Ratpositive regulation of interleukin-1 alpha production  IDA  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ccl20Ratextracellular space  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl20  (C-C motif chemokine ligand 20)
Ccr6  (C-C motif chemokine receptor 6)

Genes (Mus musculus)
Ccl20  (C-C motif chemokine ligand 20)
Ccr6  (C-C motif chemokine receptor 6)

Genes (Homo sapiens)
CCL20  (C-C motif chemokine ligand 20)
CCR6  (C-C motif chemokine receptor 6)


Additional Information