Reference - Detail
|Author||Khorooshi R, Owens T.|
|Title||Injury-induced type I IFN signaling regulates inflammatory responses in the central nervous system.|
Innate glial response is critical for the induction of inflammatory mediators and recruitment of leukocytes to sites of the injury in the CNS. We have examined the involvement of type I IFN signaling in the mouse hippocampus following sterile injury (transection of entorhinal afferents). Type I IFNs signal through a receptor (IFNAR), which involves activation of IFN regulatory factor (IRF)9, leading to the induction of IFN-stimulated genes including IRF7, that in turn enhances the induction of type I IFN. Axonal transection induced upregulation of IRF7 and IRF9 in hippocampus. Induction of IRF7 and IRF9 mRNAs was IFNAR dependent. Double-labeling immunofluorescence showed that IRF7 selectively was induced in Mac-1/CD11b(+) macrophages/microglia in hippocampus after axonal transection. IRF7 mRNA was also detected in microglia sorted by flow cytometry. Lack of type I IFN signaling resulted in increased leukocyte infiltration into the lesion-reactive hippocampus. Axonal lesion-induced CXCL10 gene expression was abrogated, whereas matrix metalloproteinase 9 mRNA was elevated in IFNAR-deficient mice. Our findings point to a role for type I IFN signaling in regulation of CNS response to sterile injury.
|MeSH||Animals Blotting, Western Brain Injuries / immunology CD11b Antigen / analysis Central Nervous System / immunology* Central Nervous System / metabolism Central Nervous System / pathology Chemokine CXCL10 / genetics Chemokine CXCL10 / immunology Chemokine CXCL10 / metabolism Female Glial Fibrillary Acidic Protein / analysis Hippocampus / injuries Hippocampus / metabolism Immunohistochemistry Inflammation / genetics Inflammation / immunology* Inflammation / metabolism Inflammation Mediators / immunology Inflammation Mediators / metabolism Interferon Regulatory Factor-7 / genetics Interferon Regulatory Factor-7 / immunology Interferon Regulatory Factor-7 / metabolism Interferon Type I / immunology* Leukocytes / immunology Leukocytes / pathology Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / immunology Matrix Metalloproteinase 9 / metabolism Mice Mice, Inbred C57BL Mice, Inbred Strains Mice, Knockout Receptor, Interferon alpha-beta / genetics Receptor, Interferon alpha-beta / immunology Receptor, Interferon alpha-beta / metabolism Reverse Transcriptase Polymerase Chain Reaction STAT1 Transcription Factor / genetics STAT1 Transcription Factor / immunology STAT1 Transcription Factor / metabolism Signal Transduction / immunology*|
|Mice||IRF-7 knockout mice C57BL/6J|