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Neuroinflammatory and Amyloidogenic Activities of IL-32β in Alzheimer's Disease.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2015 Aug; Vol. 52 (1), pp. 341-52. Date of Electronic Publication: 2014 Aug 27. - Publication Year :
- 2015
-
Abstract
- Interleukin (IL)-32β can act as either pro-inflammatory or anti-inflammatory cytokines with being dependent on the status of disease development. Herein, we investigated whether IL-32β overexpression changes cytokine levels and affects amyloid-beta (Aβ)-induced pro-inflammation in the brain. IL-32β transgenic (Tg) mice and non-Tg mice were intracerebroventricularly infused with Aβ1-42 once a day for 14 days, and then cognitive function was assessed by the Morris water maze test and passive avoidance test. Our data showed that IL-32β Tg mice increased memory impairment, glia activation, amyloidogenesis, and neuroinflammation. The expression of glial fibrillary acid protein (GFAP), Iba1, and β-secretase 1 (BACE1) in the cortex and hippocampus was much higher in the Aβ1-42-infused IL-32β Tg mice brain. The activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-κB) was much higher in Aβ1-42-infused IL-32β Tg mice brain. We also found that cytokines including IP-10, GM-CSF, JE, IL-13, and interferone-inducible T cell α chemoattractant (I-TAC) were elevated in Aβ1-42-infused IL-32β Tg mice brain. These results suggest that IL-32β could activate NF-κB and STAT3, and thus affect neuroinflammation as well as amyloidogenesis, leading to worsening memory impairment.
- Subjects :
- Alzheimer Disease complications
Amyloid Precursor Protein Secretases metabolism
Amyloid beta-Peptides metabolism
Animals
Apoptosis
Aspartic Acid Endopeptidases metabolism
Astrocytes metabolism
Astrocytes pathology
Brain metabolism
Brain pathology
Cells, Cultured
Cyclooxygenase 2 metabolism
DNA metabolism
Humans
Memory Disorders complications
Memory Disorders pathology
Mice, Transgenic
Microglia metabolism
Microglia pathology
Nitric Oxide Synthase Type II metabolism
Protein Binding
Rats
Transcription Factor RelA metabolism
Alzheimer Disease pathology
Amyloid metabolism
Inflammation pathology
Interleukins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 52
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 25159479
- Full Text :
- https://doi.org/10.1007/s12035-014-8860-0