Role of Suppressor of Cytokine Signaling 3 (SOCS3) in Altering Activated Microglia Phenotype in APPswe/PS1dE9 Mice
| Autor: | Kazuki Yokokawa, Syuuichirou Suzuki, Naotoshi Iwahara, Akihiro Matsumura, Tatsuo Manabe, Taro Saito, Jun Kawamata, Shin Hisahara, Hiromi Suzuki, Shun Shimohama, Mai Fujikura, Takashi Matsushita |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine medicine.medical_treatment Mice Transgenic Inflammation Amyloid beta-Protein Precursor 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Presenilin-1 medicine Animals Humans SOCS3 Interleukin 6 STAT3 Cells Cultured Neurons Amyloid beta-Peptides Microglia biology Interleukin-6 Tumor Necrosis Factor-alpha Suppressor of cytokine signaling 1 Chemistry General Neuroscience Brain General Medicine Cell biology Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health Clinical Psychology 030104 developmental biology medicine.anatomical_structure Cytokine Suppressor of Cytokine Signaling 3 Protein Immunology biology.protein Female Tumor necrosis factor alpha Geriatrics and Gerontology medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 55:1235-1247 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-160887 |
| Popis: | In response to changes of the central nervous system environment, microglia are capable of acquiring diverse phenotypes for cytotoxic or immune regulation and resolution of injury. Alzheimer's disease (AD) pathology also induces several microglial activations, resulting in production of pro-inflammatory cytokines and reactive oxygen species or clearance of amyloid-β (Aβ) through phagocytosis. We previously demonstrated that microglial activation and increase in oxidative stress started from the middle age in APPswe/PS1dE9 mice, and hypothesized that M1 activation occurs in middle-aged AD mice by Aβ stimulation. In the present study, we analyzed in vivo expressions of pro-inflammatory cytokines (M1 microglial markers), M2 microglial markers, and suppressor of cytokine signaling (SOCS) family, and examined the microglial phenotypic profile in APPswe/PS1dE9 mice. Then we compared the in vitro gene expression patterns of Aβ- and lipopolysaccharide (LPS)-stimulated primary-cultured microglia. Microglia in APPswe/PS1dE9 mice exhibited an M1-like phenotype, expressing tumor necrosis factor α (TNFα) but not interleukin 6 (IL6). Aβ-stimulated primary-cultured microglia also expressed TNFα but not IL6, whereas LPS-stimulated primary-cultured microglia expressed both pro-inflammatory cytokines. Furthermore, both microglia in APPswe/PS1dE9 mice and Aβ-stimulated primary-cultured microglia expressed SOCS3. Reduction of SOCS3 expression in Aβ-challenged primary-cultured microglia resulted in upregulation of IL6 expression. Our findings indicate that SOCS3 suppresses complete polarization to M1 phenotype through blocking IL6 production, and Aβ-challenged primary-cultured microglia replicate the in vivo gene expression pattern of microglia in APPswe/PS1dE9 mice. Aβ may induce the M1-like phenotype through blocking of IL6 by SOCS3. |
| Databáze: | OpenAIRE |
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