Regulation of pro-inflammatory responses by S100A9 (P6124)

Abstract

Abstract Several Damage-Associated Molecular Patterns have been known to play an important role in inflammation. However, whether DAMPs are involved in lung inflammation during infection is not clear. In order to examine the important mechanisms of DAMPs during virus infection, influenza A virus infection model was used to study the role of S100A9, one of DAMPs, during lung pathogenesis. Here, we show that S100A9 is induced and secreted from flu-infected macrophages via a “non-damage” pathway. Since DAMPs are known to activate pro-inflammatory responses, we next examined whether purified recombinant S100A9 protein triggers pro-inflammatory responses in macrophages. Indeed, treatment of macrophages with S100A9 resulted in production of pro-inflammatory cytokines. The role of S100A9 during flu infection was also assessed by studying production of S100A9 in the respiratory tract of flu-infected mice. Upon flu infection, the production of S100A9 was induced in the lung and bronchoalveolar fluid. Moreover, the pro-inflammatory activity of extracellular S100A9 in the airway was obvious from robust production of pro-inflammatory cytokines in the lung. Thus our studies have identified S100A9 as a potent activator of pro-inflammatory response in macrophages and in the respiratory tract of mice. In addition, we uncovered ability of flu to induce S100A9 expression and production in macrophages and in the lung.