title: Differential pathways for interleukin-1β production activated by chromogranin A and amyloid β in microglia.
abstract: Although chromogranin A (CGA) is frequently present in Alzheimer's disease (AD), senile plaques associated with microglial activation, little is known about basic difference between CGA and fibrillar amyloid-β (fAβ) as neuroinflammatory factors. Here we have compared the interleukin-1β (IL-1β) production pathways by CGA and fAβ in microglia. In cultured microglia, production of IL-1β was induced by CGA, but not by fAβ. CGA activated both nuclear factor-κB (NF-κB) and pro-caspase-1, whereas fAβ activated pro-caspase-1 only. For the activation of pro-caspase-1, both CGA and fAβ needed the enzymatic activity of cathepsin B (CatB), but only fAβ required cytosolic leakage of CatB and the NLRP3 inflammasome activation. In contrast, fAβ induced the IL-1β secretion from microglia isolated from the aged mouse brain. In AD brain, highly activated microglia, which showed intense immunoreactivity for CatB and IL-1β, surrounded CGA-positive plaques more frequently than Aβ-positive plaques. These observations indicate differential pathways for the microglial IL-1β production by CGA and fAβ, which may aid in better understanding of the pathological significance of neuroinflammation in AD.
authors.affiliation: Faculty of Dental Sciences, Department of Aging Science and Pharmacology, Kyushu University, Fukuoka, Japan. Electronic address: zhouw@dent.kyushu-u.ac.jp.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hashioka
authors.forename: Sheng
authors.initials: S
authors.lastname: Yu
authors.forename: Claudia
authors.initials: C
authors.lastname: Schwab
authors.forename: Ryo
authors.initials: R
authors.lastname: Okada
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Patrick L
authors.initials: PL
authors.lastname: McGeer
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002401:Cathepsin B / Q000502:physiology; D002478:Cells, Cultured; D053379:Chromogranin A / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D058225:Plaque, Amyloid / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D053379:Chromogranin A; D058847:Inflammasomes; D053583:Interleukin-1beta; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D002401:Cathepsin B; D020170:Caspase 1
keywords: Alzheimer's disease; Amyloid β protein; Cathepsin B; Chromogranin A; Interleukin-1β; Microglia; Nuclear factor-κB; Toll-like receptor 4