β-Amyloid (25-35) Peptide and IFN-γ Synergistically Induce the Production of the Chemotactic Cytokine MCP-1/JE in Monocytes and Microglial Cells

Lucia Meda, Sergio Bernasconi, Corrada Bonaiuto, Silvano Sozzani, Dan Zhou, Laszlo Otvos, Alberto Mantovani, Filippo Rossi, Marco A. Cassatella

Research output: Contribution to journalArticle

Abstract

The molecular mechanisms involved in the development of senile plaques characteristic of aging and Alzheimer's disease are poorly understood. In this study, we examined whether human monocytes and murine microglial cells stimulated with the active fragment of amyloid β-protein (Aβ(25-35)) express the monocyte chemotactic protein-1 (MCP-1)/JE. We show that upon incubation with Aβ(25-35), human monocytes accumulate MCP-1 mRNA and produce significant amounts of MCP-1. The effect of Aβ(25-35) on MCP-1 secretion was neither mimicked by a scrambled analogue nor affected by polymyxin B sulfate, even though the latter almost completely abolished the effect of LPS on MCP-1 expression. Murine microglial cells stimulated with Aβ(25-35) also expressed high levels of JE mRNA (the murine counterpart of MCP-1) and released bioactive chemotactic factors. In addition, we report that IFN-γ significantly synergizes with Aβ(25-35) either in human monocytes or in murine microglial cells, and that Aβ(25-35) plus/minus IFN-γ-mediated early induction of MCP-1 mRNA does not require new protein synthesis. Finally, we provide evidence that the Aβ(25-35)- and Aβ plus IFN-γ-induced production of MCP-1 is, in large part, mediated in an autocrine fashion by endogenous TNF-α. Taken together, our findings uncover another novel biologic action of Aβ(25-35) and might help in better understanding the mechanisms underlying mononuclear phagocyte recruitment and activation into amyloid deposits.

Original languageEnglish
Pages (from-to)1213-1218
Number of pages6
JournalJournal of Immunology
Volume157
Issue number3
Publication statusPublished - Aug 1 1996

ASJC Scopus subject areas

  • Immunology

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