S100A8/A9 and S100A9 reduce acute lung injury

Area of Science:

• Immunology
• Pulmonary Medicine
• Molecular Biology

Background:

• S100A8 and S100A9 are myeloid cell proteins implicated in inflammatory lung diseases.
• Their roles in inflammation are complex, with both pro- and anti-inflammatory effects reported.
• Previous studies suggest activation of Toll-like receptor 4 (TLR4), but direct in vivo comparisons are limited.

Purpose of the Study:

• To systematically compare the in vivo effects of S100A9 and S100A8/A9 inhalation on lung inflammation in mice.
• To investigate the specific inflammatory mediators and pathways influenced by these S100 proteins.

Main Methods:

• Inhalation of S100A9 or S100A8/A9 in a murine lung model.
• Assessment of neutrophil and lymphocyte influx, mast cell degranulation, and chemokine gene expression (e.g., CXCL-10).
• Measurement of pro-inflammatory mediators (TNF-α, IL-1β, IL-6, SAA3) and S100A8/IL-10 mRNA/protein.
• Evaluation of protective effects against lipopolysaccharide (LPS)-induced acute lung injury.

Main Results:

• S100A9 inhalation induced mild neutrophil and lymphocyte influx, associated with mast cell degranulation and CXCL-10 upregulation.
• Neither S100A9 nor S100A8/A9 significantly induced key pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) or SAA3.
• Both S100A9 and S100A8/A9 reduced neutrophil influx in LPS-induced lung injury, though less effectively than S100A8.
• Common protective pathways identified include increased sirtuin-1 (NAD+-dependent protein deacetylase) and STAT3 activation, potentially reducing NF-κB signaling.

Conclusions:

• S100A9 exhibits distinct inflammatory properties compared to S100A8 in the murine lung.
• These S100 proteins play a role in maintaining lung homeostasis and protective mechanisms.
• Novel pathways involving sirtuin-1 and STAT3 activation contribute to the anti-inflammatory effects of S100 proteins in acute lung injury.