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

• Published in: FEBS letters Vol. 588; no. 13; pp. 2141 - 2146
• Main Authors: Simard, Jean-Christophe, Noël, Claudie, Tessier, Philippe A., Girard, Denis
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 13.06.2014; Wiley
• Subjects: Calgranulin A - metabolism; Calgranulin B - metabolism; CREB-1; Cyclic AMP Response Element-Binding Protein - metabolism; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Human health and pathology; Humans; I-kappa B Kinase - metabolism; Immunity, Innate - drug effects; Infectious diseases; Inflammation Mediators - metabolism; Interleukin-8 - biosynthesis; Life Sciences; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophil; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - metabolism; NF-kappa B - metabolism; NF-κB; Recombinant Proteins - metabolism; S100A9; STAT-3; STAT-5; STAT3 Transcription Factor - metabolism; STAT5 Transcription Factor - metabolism; Toxicology; Transcription Factors - metabolism; CREB-1; NF-κB; STAT-3; Neutrophil; STAT-5; S100A9
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2014.04.027

•S100A9 does not increase cytokine production by itself in human neutrophils.•S100A9 primes neutrophils to GM-CSF- or fMLP-induced cytokine production.•A different set of transcription factors is involved in the priming effect of S100A9 in response to GM-CSF or fMLP. Inflammation is highly regulated by various agents. Unexpectedly, we report here that the damage-associated molecular pattern S100A9 protein, a potent neutrophil activator and inducer of cytokine production in monocytes, is not a direct activator of cytokine production in human neutrophils. However, S100A9 primed IL-8 production in fMLP- and GM-CSF-stimulated neutrophiles via NF-κB and CREB-1, and NF-κB, 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.