Serum amyloid A-induced mRNA expression and release of tumor necrosis factor-alpha (TNF-alpha) in human neutrophils.

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.