title: S100A8/A9 and S100A9 reduce acute lung injury.
abstract: S100A8 and S100A9 are myeloid cell-derived proteins that are elevated in several types of inflammatory lung disorders. Pro- and anti-inflammatory properties are reported and these proteins are proposed to activate TLR4. S100A8 and S100A9 can function separately, likely through distinct receptors but a systematic comparison of their effects in vivo are limited. Here we assess inflammation in murine lung following S100A9 and S100A8/A9 inhalation. Unlike S100A8, S100A9 promoted mild neutrophil and lymphocyte influx, possibly mediated in part, by increased mast cell degranulation and selective upregulation of some chemokine genes, particularly CXCL-10. S100 proteins did not significantly induce proinflammatory mediators including TNF-α, interleukin-1β (IL-1β), IL-6 or serum amyloid A3 (SAA3). In contrast to S100A8, neither preparation induced S100A8 or IL-10 mRNA/protein in airway epithelial cells, or in tracheal epithelial cells in vitro. Like S100A8, S100A9 and S100A8/A9 reduced neutrophil influx in acute lung injury provoked by lipopolysaccharide (LPS) challenge but were somewhat less inhibitory, possibly because of differential effects on expression of some chemokines, IL-1β, SAA3 and IL-10. Novel common pathways including increased induction of an NAD+-dependent protein deacetylase sirtuin-1 that may reduce NF-κB signalling, and increased STAT3 activation may reduce LPS activation. Results suggest a role for these proteins in normal homeostasis and protective mechanisms in the lung.
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hsu
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Nicodemus
authors.initials: N
authors.lastname: Tedla
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Sze Wing
authors.initials: SW
authors.lastname: Wong
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Sharron
authors.initials: S
authors.lastname: Chow
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kawaguchi
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Geczy
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D054357:Chemokine CXCL10 / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D010766:Phosphorylation; D009418:S100 Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D054357:Chemokine CXCL10; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009418:S100 Proteins