S100A9 Exacerbates the A beta 1-42-mediated Innate Immunity in Human THP-1 Monocytes

Abstract

The S100A9 protein is an important proinflammatory factor of innate immunity that has been proposed to participate in inflammation associated with the pathogenesis of Alzheimer's disease. Here, we provide insights into the potential roles of extracellular S100A9 in the interaction with the immune response in human THP-1 monocytic cells that have been challenged with amyloid beta 1-42 (A beta 1-42) monomers instead of oligomers. Extracellular S100A9 alone produced a stimulatory effect on tumor necrosis factor-alpha and interleukin-1 beta, expression as well as released monocyte chemoattractant protein-1 into culture supernatants, which was accompanied by an increased level of matrix metalloproteinas-9 activity. Importantly, co-stimulation with S100A9 and A beta 1-42 resulted in a marked enhancement of A beta 1-42-mediated release of these proinflammatory mediators under the same experimental conditions, whereas heat inactivated S100A9 had little effect. Our findings clearly suggest that excess S100A9 protein may play an important role in the pathological processes of Alzheimer's disease by exacerbating the A beta 1-42-induced innate immune response.