title: Neuroinflammatory and Amyloidogenic Activities of IL-32β in Alzheimer's Disease.
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.
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.forename: Jin A
authors.initials: JA
authors.lastname: Kim
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Hwang
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Myung Ki
authors.initials: MK
authors.lastname: Baek
authors.forename: Jin Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Hong
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Ki Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Choi
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007378:Interleukins / Q000378:metabolism*; D008569:Memory Disorders / Q000150:complications / Q000473:pathology; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; C496971:IL32 protein, human; D007378:Interleukins; D051996:Transcription Factor RelA; D004247:DNA; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse