Astrocyte‐targeted IL‐10 production decreases proliferation and induces a downregulation of activated microglia/macrophages after PPT
Autor: | Bernardo Castellano, Berta González, Kalpana Shrivastava, Beatriz Almolda, Mireia Recasens |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Transgene Perforant Pathway Population Down-Regulation Mice Transgenic Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation Glial Fibrillary Acidic Protein medicine Animals education Cell Proliferation education.field_of_study Microglia biology Macrophages Monocyte Macrophage Activation Interleukin-10 Cell biology Mice Inbred C57BL Disease Models Animal Interleukin 10 030104 developmental biology medicine.anatomical_structure Bromodeoxyuridine Neurology Integrin alpha M Astrocytes Brain Injuries biology.protein Cytokines 030217 neurology & neurosurgery Astrocyte |
Zdroj: | Glia. |
ISSN: | 1098-1136 0894-1491 |
Popis: | When central nervous system (CNS) homeostasis is altered, microglial cells become rapidly activated, proliferate and release a broad range of molecules. Among the plethora of molecules involved in the regulation of microglial activation, cytokines are considered crucial. Although production of interleukin-10 (IL-10) has been demonstrated after different types of CNS injuries and associated with protective functions, the specific role played by IL-10 modulating microglial cells remains unclear. Hence, the objective of this study was to evaluate the effects of transgenic astrocyte IL-10 production on microglial activation associated with axonal anterograde degeneration. To address it, the hippocampal area subjected to perforant pathway transection (PPT) was analyzed by immunohistochemistry (IHC), flow cytometry and protein microarray in transgenic (GFAP-IL10Tg) mice and their corresponding wild types (WT) littermates. Our results demonstrated increased microglial/macrophages density in nonlesioned and PPT-lesioned GFAP-IL10Tg animals when compared with nonlesioned and lesioned WT, respectively. This increase was not due to proliferation, as GFAP-IL10Tg mice showed a reduced proliferation of microglial cells, but was related to an increased population of CD11b+/CD45high monocyte/macrophages. Despite this higher number, the microglia/macrophage population in transgenic animals displayed a downregulated phenotype characterized by lower MHCII, ICOSL, and CD11c. Moreover, a sustained T-cell infiltration was found in transgenic animals. We strongly suggest these modifications must be associated with indirect effects derived from the influence of IL-10 on astrocytes and/or neurons, which express IL-10R. We finally suggested that TGF-β produced by astrocytes, along with IL-2 and CXCL10 might be crucial molecules mediating the effects of transgenic IL-10. |
Databáze: | OpenAIRE |
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