Human S100A9 potentiates IL-8 production in response to GM-CSF or fMLP via activation of a different set of transcription factors in neutrophils

Inflammation is highly regulated by various agents. Unexpectedly, we report here that the damageassociated molecular pattern S100A9 protein, a potent neutrophil activator and inducer of cytokine production in monocytes, is not a direct activator of cytoldne production in human neutrophils. However, S100A9 primed IL-8 production in fMLP-and GM-CSF-stimulated neutrophiles via NF-kappa B and CREB-1, and NF-kappa B, STAT3 and STAT5, respectively. Pharmacological inhibition confirmed the importance of these transcription factors by significantly decreasing IL-8 production. This is the first time that a different set of transcription factors are shown to be involved in S100A9-primed neutrophils in response to proinflammatory agonist. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.