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Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination.

ABSTRACT: The functional role of the ELR(+) chemokine CXCL1 in host defense and disease following infection of the CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was examined. Mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells were generated and this allowed for selectively increasing CNS expression of CXCL1 in response to JHMV infection and evaluating the effects on neuroinflammation, control of viral replication, and demyelination. Inducible expression of CNS-derived CXCL1 resulted in increased levels of CXCL1 protein within the serum, brain, and spinal cord that correlated with increased frequency of Ly6G(+)CD11b(+) neutrophils present within the CNS. Elevated levels of CXCL1 did not influence the generation of virus-specific T cells, and there was no difference in control of JHMV replication compared with control mice, indicating that T cell infiltration into the CNS is CXCL1-independent. Sustained CXCL1 expression within the CNS resulted in increased mortality that correlated with elevated neutrophil infiltration, diminished numbers of mature oligodendrocytes, and an increase in the severity of demyelination. Neutrophil ablation in CXCL1-transgenic mice reduced the severity of demyelination in mice, arguing for a role for these cells in white matter damage. Collectively, these findings illustrate that sustained CXCL1 expression amplifies the severity of white matter damage and that neutrophils can contribute to this process in a model of viral-induced neurologic disease.

SUBMITTER: Marro BS

PROVIDER: S-EPMC4742654 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination.

Marro Brett S BS Grist Jonathan J JJ Lane Thomas E TE

Journal of immunology (Baltimore, Md. : 1950) 20160115 4

The functional role of the ELR(+) chemokine CXCL1 in host defense and disease following infection of the CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was examined. Mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells were generated and this allowed for selectively increasing CNS expression of CXCL1 in response to JHMV infection and evaluating the effects on neuroinflammation ...[more]

PMID: 26773148

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Dataset Information

Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination.

Publications

Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination.

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