Role of S100A9 in the development of neutrophilic inflammation in asthmatics and in a murine model

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2017-10, Vol.183, p.158-166
• Main Authors: Lee, Tae-Hyeong, Chang, Hun Soo, Bae, Da-Jeong, Song, Hyun Ji, Kim, Myung-Sin, Park, Jong Sook, Jun, Ji Ae, Lee, Si Young, Uh, Soo Taek, Kim, Soo Hyun, Park, Choon-Sik
• Format: Article
• Language: English
• Subjects: Adult; Animals; Antibodies, Neutralizing - pharmacology; Asthma; Asthma - immunology; Asthma - physiopathology; Calgranulin B; Calgranulin B - immunology; Disease Models, Animal; Female; Humans; IFN-γ; IL-17; IL-1β; Inflammation; Interferon-gamma - drug effects; Interferon-gamma - immunology; Interleukin-17 - immunology; Interleukin-1beta - drug effects; Interleukin-1beta - immunology; Leukocyte Elastase - metabolism; Male; Mice; Middle Aged; Neutrophils - drug effects; Neutrophils - immunology; S100A9; Sputum - chemistry; Sputum - immunology
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2017.08.013

S100A9 is an endogenous danger signal that promotes and exacerbates the neutrophilic inflammatory response. To investigate the role of S100A9 in neutrophilic asthma, S100A9 levels were measured in sputum from 101 steroid-naïve asthmatics using an ELISA kit and the levels were significantly correlated with percentages of neutrophils in sputum. Intranasal administration of recombinant S100A9 markedly increased neutrophil numbers at 8h and 24h later with concomitant elevation of IL-1β, IL-17, and IFN-γ levels. Treatment with an anti-S100A9 antibody restored the increased numbers of neutrophils and the increased airway resistance in OVA/CFA mice toward the levels of sham-treated mice. Concomitantly, the S100A9 and neutrophil elastase double positive cells were markedly reduced with attenuation of IL-1β, IL-17, and IFN-γ levels by the treatment with the anti-S100A9 antibody. Our data support a role of S100A9 to initiate and amplify the neutrophilic inflammation in asthma, possibly via inducing IL-1β, IL-17 and IFN-γ. •S100A9 is an endogenous danger signal that promotes and exacerbates the neutrophilic inflammatory response.•Our data support a role of S100A9 to initiate and amplify the neutrophilic inflammation via inducing IL-1β, IL-17 and IFN-γ.•Modulation of S100A9 in the airway may be a therapeutic strategy to control neutrophilic inflammation in asthma.