title: Impaired degradation of serum amyloid A (SAA) protein by cytokine-stimulated monocytes.
abstract: Secondary amyloidosis (AA amyloidosis) is a systemic disease characterized by the extracellular tissue deposition of insoluble amyloid A (AA) protein. Aberrant metabolism of serum amyloid A (SAA) by macrophages is only one of many putative mechanisms which may be important in AA amyloidogenesis. In this study, we investigated the effects of cytokines on human monocyte-mediated SAA proteolysis. Human peripheral blood mononuclear cells (PBMC) or CD14(+) monocytes were cultured with SAA, and the culture supernatants were then subjected to anti-SAA immunoblot. CD14(+) monocytes degraded SAA completely. Whereas, when CD14(+) monocytes were pretreated with IL-1 beta or IFN-gamma, increasing amounts of SAA-related derivatives were detected in culture supernatants. These findings suggest that activation of monocytes by IL-1 beta or IFN-gamma hampers the proteolysis of a precursor protein and leads to a partial degradation of SAA. This down-regulated proteolysis of SAA protein by cytokine-stimulated monocytes may play a role in the mechanism of AA amyloid formation as well as its removal.
authors: The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. eguchi@net.nagasaki-u.ac.jp
authors: K
authors: K
authors: Migita
authors: S
authors: S
authors: Yamasaki
authors: K
authors: K
authors: Shibatomi
authors: H
authors: H
authors: Ida
authors: M
authors: M
authors: Kita
authors: A
authors: A
authors: Kawakami
authors: K
authors: K
authors: Eguchi
mesh_terms: D000686:Amyloidosis / Q000209:etiology; D001053:Apolipoproteins / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000378:metabolism*
chemical_list: D001053:Apolipoproteins; D016207:Cytokines; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D000685:Serum Amyloid A Protein; D007371:Interferon-gamma