Premium
Amyloid β and Amylin Fibrils Induce Increases in Proinflammatory Cytokine and Chemokine Production by THP‐1 Cells and Murine Microglia
Author(s) -
Yates Stephen L.,
Burgess Loyd H.,
KocsisAngle June,
Antal Joyce M.,
Dority Michael D.,
Embury Paula B.,
Piotrkowski Anthony M.,
Brunden Kurt R.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741017.x
Subject(s) - microglia , amylin , proinflammatory cytokine , chemokine , cytokine , tumor necrosis factor alpha , neuroinflammation , amyloid (mycology) , senile plaques , interleukin , inflammation , chemistry , biology , endocrinology , immunology , medicine , alzheimer's disease , inorganic chemistry , disease , islet , insulin
Activated microglia surrounding amyloid β‐containing senile plaques synthesize interleukin‐1, an inflammatory cytokine that has been postulated to contribute to Alzheimer's disease pathology. Studies have demonstrated that amyloid β treatment causes increased cytokine release in microglia and related cell cultures. The present work evaluates the specificity of this cellular response by comparing the effects of amyloid β to that of amylin, another amyloidotic peptide. Both lipopolysaccharide‐treated THP‐1 monocytes and mouse microglia showed significant increases in mature interleukin‐1β release 48 h following amyloid β or human amylin treatment, whereas nonfibrillar rat amylin had no effect on interleukin‐1β production by THP‐1 cells. Lipopolysacharide‐stimulated THP‐1 cells treated with amyloid β or amylin also showed increased release of the proinflamatory cytokines tumor necrosis factor‐α and interleukin‐6, as well as the chemokines interleukin‐8 and macrophage inflammatory protein‐1 α and ‐1β. THP‐1 cells incubated with fibrillar amyloid β or amylin in the absence of lipopolysaccharide also showed significant increases of both interleukin‐1β and tumor necrosis factor‐α mRNA. Furthermore, treatment of THP‐1 cells with amyloid fibrils resulted in an elevated expression of the immediate‐early genes c‐ fos and junB . These studies provide further evidence that fibrillar amyloid peptides can induce signal transduction pathways that initiate an inflammatory response that is likely to contribute to Alzheimer's disease pathology.