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: (View Article at PubMed) PMID:19428685
DOI: Full-text: DOI:10.1016/j.neures.2009.01.017

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.

Disease Annotations    

Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

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

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

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

Additional Information