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High glucose induces pro‐inflammatory phenotype in human astrocytes and enhances neurotoxicity
Author(s) -
Bahniwal Manpreet,
Little Jonathan P.,
Klegeris Andis
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.691.8
Subject(s) - neuroinflammation , microglia , proinflammatory cytokine , astrocyte , neurotoxicity , endocrinology , medicine , stat protein , neurodegeneration , stat1 , interleukin 6 , chemistry , inflammation , cancer research , biology , stat3 , phosphorylation , microbiology and biotechnology , central nervous system , toxicity , disease , receptor
Chronic neuroinflammation caused by activation of microglia and astrocytes in the brain contributes to neuronal loss and disease progression in Alzheimer's disease (AD). High glucose has been shown to increase release of pro‐inflammatory mediators from various immune cells, including microglia. We investigated the effects of glucose (5.5–30.5 mM) on astrocytic cells. High glucose increased expression and secretion of pro‐inflammatory cytokines interleukin (IL)‐6 and IL‐8 (P<0.05) in human primary astrocytes and U‐118 MG astrocytoma cells. This astrocytic proinflammatory response to elevated glucose may involve increased phosphorylation of the signal transducer and activator of transcription (STAT)‐3. High glucose also increased the susceptibility of human SH‐SY5Y neuroblastoma cells to toxicity induced by hydrogen peroxide and Alzheimer amyloid‐β1–42 (P<0.05). We hypothesize that brain hyperglycemia in type 2 diabetes contributes to the observed increased risk of AD by exacerbating astrocyte‐mediated neuroinflammation and neuronal injury caused by disease‐specific agents.