title: S100A9 Exacerbates the Aβ1-42-mediated Innate Immunity in Human THP-1 Monocytes.
abstract: The S100A9 protein is an important proinflammatory factor of innate immunity that has been proposed to participate in inflammation associated with the pathogenesis of Alzheimer's disease. Here, we provide insights into the potential roles of extracellular S100A9 in the interaction with the immune response in human THP-1 monocytic cells that have been challenged with amyloid β1-42 (Aβ1-42) monomers instead of oligomers. Extracellular S100A9 alone produced a stimulatory effect on tumor necrosis factor-α and interleukin-1β, expression as well as released monocyte chemoattractant protein-1 into culture supernatants, which was accompanied by an increased level of matrix metalloproteinas-9 activity. Importantly, co-stimulation with S100A9 and Aβ1-42 resulted in a marked enhancement of Aβ1-42-mediated release of these proinflammatory mediators under the same experimental conditions, whereas heat inactivated S100A9 had little effect. Our findings clearly suggest that excess S100A9 protein may play an important role in the pathological processes of Alzheimer's disease by exacerbating the Aβ1-42-induced innate immune response.
authors: Kyoung A
authors: KA
authors: Jhang
authors: Eun Ok
authors: EO
authors: Lee
authors: Hee-Sun
authors: HS
authors: Kim
authors: Keun-A
authors: KA
authors: Chang
authors: Yoo-Hun
authors: YH
authors: Suh
authors: Department of Microbiology, School of Medicine, Ewha Womans University, 911-1, Mok-6-dong, Yangcheonku, Seoul, Korea, 158-710. younghae@ewha.ac.kr.
authors: Young Hae
authors: YH
authors: Chong
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D040502:Calgranulin B / Q000494:pharmacology*; D002461:Cell Line, Transformed; D018932:Chemokine CCL2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D053583:Interleukin-1beta / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C111835:CCL2 protein, human; D040502:Calgranulin B; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D020780:Matrix Metalloproteinase 9