S100 proteins regulate LPS-induced inflammation in murine lung — ASN Events
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  2. Poster Session 1
  3. S100 proteins regulate LPS-induced inflammation in murine lung

S100 proteins regulate LPS-induced inflammation in murine lung (#79)

Yuka Hiroshima 1 , Kenneth Hsu 1 , Nicodemus Tedla 1 , Sharron Chow 1 , Naomi Kawaguchi 1 , Carolyn L Geczy 1
  1. University New South Wales, Sydney, NSW, Australia

Aims: S100A8 and S100A9 are calcium binding proteins that comprise ~40% of the neutrophil cytosol and induced in several cell types by inflammatory mediators or by oxidative stress. The S100A8/S100A9 heterocomplex is found in high levels in most inflammatory diseases, including inflammatory lung diseases. S100A8 and S100A9 are considered proinflammatory by activating TLR4 and/or the receptor for advanced glycation end products (RAGE). We aimed to define effects of S100A8, S100A9 and S100A8/A9, and how they regulate LPS-induced acute lung injury (ALI) in mice.

Methods: Intranasally delivered LPS-minimized pure preparations of recombinant S100A8 and S100A9 were used to compare pulmonary responses to LPS. Inflammation-associated genes were compared by qPCR, cytokine levels in brochoalveolar lavage fluid (BALF) quantitated by ELISA and IL-10 in lung sections by immunohistochemistry (IHC). Primary tracheal epithelial cells (EC) were used to assess responses in vitro.

Results: S100A8 promoted high IL-10 mRNA expression in lungs harvested 12 h after inhalation. IL-10 in BALF reflected these differences and IHC confirmed strong expression in airway epithelial cells at 12 h. S100A9 and S100A8/A9 produced only low levels of IL-10 in BALF 1 h and 4 h post-challenge. Only S100A8 induced IL-10 mRNA in EC in vitro. S100A8 and S100A9 suppressed neutrophil infiltration in response to intranasal LPS challenge, and reduced LPS-induced cytokine and chemokine genes. Only S100A8/A9 enhanced IL-1ß mRNA expression and levels in BALF, compared to LPS-treated mice, and the complex did not suppress LPS-provoked neutrophil influx.

Conclusions: S100A8 and S100A9 did not activate TLR4 or RAGE. S100A8 promoted high IL-10 expression in airway epithelial cells and strongly suppressed LPS-induced inflammation. S100A8 also protects against oxidative stress and may attenuate ALI via IL-10 and redox-modulation. Comparatively, S100A9 and S100A8/A9 were less immunosuppressive than S100A8.

Support: Funded by grants #630647 and #1027189, NHMRC Australia.