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PMID:12857601

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Citation

Ribeiro, FP, Furlaneto, CJ, Hatanaka, E, Ribeiro, WB, Souza, GM, Cassatella, MA and Campa, A (2003) mRNA expression and release of interleukin-8 induced by serum amyloid A in neutrophils and monocytes. Mediators Inflamm. 12:173-8

Abstract

The acute phase response is a systemic reaction to inflammatory processes characterized by multiple physiological adaptations, including the hepatic synthesis of acute-phase proteins. In humans, serum amyloid A (SAA) is one of the most prominent of these proteins. Despite the huge increase of serum levels of SAA in inflammation, its biological role remains to be elucidated, even though SAA is undoubtedly active in neutrophils. In a previous study, we reported that SAA induces the release of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-8 from human blood neutrophils. Here, we extend our earlier study, focusing on the effect of SAA on neutrophil IL-8 transcription and on the signaling pathways involved. We demonstrate herein that SAA, in relatively low concentrations (0.4-100 microg/ml) compared with those found in plasma in inflammatory conditions, induces a dose-dependent release of IL-8 from neutrophils. The p38 mitogen-activated protein kinase inhibitor SB 203580 inhibits the IL-8 mRNA expression and the release of protein from neutrophils. The release of IL-8 from SAA-stimulated neutrophils is strongly suppressed by the addition of N-acetyl-l-cysteine, alpha-mercaptoethanol, glutathione, and dexamethasone. SAA also induces IL-8 expression and release from monocytes. In conclusion, SAA appears to be an important mediator of the inflammatory process, possibly contributing to the pool of IL-8 produced in chronic diseases, which may play a role in degenerative diseases.

Links

PubMed PMC1781605 Online version:10.1080/0962935031000134897

Keywords

Dose-Response Relationship, Drug; Humans; Interleukin-8/genetics; Interleukin-8/metabolism; Monocytes/metabolism; Neutrophils/metabolism; Osmolar Concentration; RNA, Messenger/metabolism; Serum Amyloid A Protein/administration & dosage; Serum Amyloid A Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SAA1

involved_in

GO:0001819: positive regulation of cytokine production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SAA1

involved_in

GO:0032732: positive regulation of interleukin-1 production

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SAA1

involved_in

GO:0050716: positive regulation of interleukin-1 secretion

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SAA1

involved_in

GO:0050715: positive regulation of cytokine secretion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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