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Published on: July 20, 2019
Serum amyloid A-induced mRNA expression and release of tumor necrosis factor-alpha (TNF-alpha) in human neutrophils
Elaine Hatanaka1, Cristiane J Furlaneto, Fernanda P Ribeiro
1Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP CEP 05508-900, Brazil. ehata@usp.br
Abstract:
Recently, we described the effect of the acute phase protein serum amyloid A (SAA) on the mRNA expression and release of IL-8 in neutrophils [Mediators Inflamm. 12 (3) (2003) 173]. Here, we expand this earlier study, focusing on tumor necrosis factor-alpha (TNF-alpha) m-RNA expression and protein release. Our findings indicate that SAA stimulates the rapid expression and release of TNF-alpha from cultured human blood neutrophils. The release of TNF-alpha from SAA-stimulated neutrophils is strongly suppressed by the addition of the antioxidants N-acetyl-L-cysteine, alpha-mercaptoethanol, glutathione, the antiinflammatory dexamethasone and the compounds wortmannin (a PI3K inhibitor), PD98059 (a MEK-1 inhibitor) and SB203580 (a p38 inhibitor). Monocytes also responded to SAA by releasing TNF-alpha. These data are congruent with the increasing evidence of the role of SAA in modulating inflammatory and immune responses, possibly contributing to the pool of cytokines produced in acute inflammation and in chronic diseases.
Insights
Serum amyloid A (SAA) protein stimulates tumor necrosis factor-alpha (TNF-alpha) release from neutrophils and monocytes. This release is inhibited by antioxidants and specific signaling pathway inhibitors, highlighting SAA's role in inflammation.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Serum amyloid A (SAA) is an acute phase protein with known roles in inflammation.
- Previous research established SAA's effect on IL-8 expression in neutrophils.
Purpose of the Study:
- To investigate the impact of SAA on tumor necrosis factor-alpha (TNF-alpha) mRNA expression and protein release.
- To identify signaling pathways and molecules involved in SAA-induced TNF-alpha release.
Main Methods:
- Cultured human blood neutrophils and monocytes were stimulated with SAA.
- mRNA expression and protein release of TNF-alpha were measured.
- The effects of antioxidants, dexamethasone, and specific kinase inhibitors (wortmannin, PD98059, SB203580) on TNF-alpha release were assessed.
Main Results:
- SAA significantly stimulated rapid TNF-alpha mRNA expression and protein release from neutrophils.
- Monocytes also released TNF-alpha in response to SAA.
- TNF-alpha release was markedly suppressed by antioxidants (N-acetyl-L-cysteine, alpha-mercaptoethanol, glutathione), dexamethasone, and inhibitors of PI3K, MEK-1, and p38 MAPK pathways.
Conclusions:
- SAA is a potent stimulator of TNF-alpha production in neutrophils and monocytes.
- The release of TNF-alpha induced by SAA involves reactive oxygen species and signaling pathways including PI3K, MEK-1, and p38 MAPK.
- SAA plays a significant role in modulating immune and inflammatory responses, potentially contributing to acute and chronic inflammatory conditions.
