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

Abstract S100A9is an endogenous danger signal that promotes and exacerbates the neutrophilicinflammatory response. To investigate the role of S100A9in neutrophilicasthma, S100A9levels were measured in sputumfrom 101 steroid-naive asthmatics using an ELISA kit and the levels were significantly correlated with percentages of neutrophilsin sputum. Intranasal administration of recombinant S100A9markedly increased neutrophilnumbers at 8 h and 24 h later with concomitant elevation of IL-1β, IL-17, and IFN-γ levels. Treatment with an anti- S100A9antibody restored the increased numbers of neutrophilsand the increased airway resistancein OVA/CFA mice toward the levels of sham-treated mice. Concomitantly, the S100A9and neutrophil elastasedouble positive cells were markedly reduced with attenuation of IL-1β, IL-17, and IFN-γ levels by the treatment with the anti- S100A9antibody. Our data support a role of S100A9to initiate and amplify the neutrophilicinflammation in asthma, possibly via inducing IL-1β, IL-17 and IFN-γ.