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- Title
S100A9 blockade prevents lipopolysaccharide-induced lung injury via suppressing the NLRP3 pathway.
- Authors
Zhao, Boying; Lu, Renfu; Chen, Jianjun; Xie, Ming; Zhao, Xingji; Kong, Lingwen
- Abstract
<bold>Background: </bold>S100 calcium binding protein A9 (S100A9) is a pro-inflammatory alarmin associated with several inflammation-related diseases. However, the role of S100A9 in lung injury in sepsis has not been fully investigated. Therefore, the present study aimed to determine the role of S100A9 in a lipopolysaccharide (LPS)-induced lung injury murine model and its underlying molecular mechanisms.<bold>Methods: </bold>LPS was utilized to induce sepsis and lung injury in C57BL/6 or NOD-like receptor family pyrin domain containing 3 (NLRP3)-/- mice. To investigate the effects of S100A9 blockade, mice were treated with a specific inhibitor of S100A9. Subsequently, lung injury and inflammation were evaluated by histology and enzyme‑linked immunosorbent assay (ELISA), respectively. Furthermore, western blot analysis and RT-qPCR were carried out to investigate the molecular mechanisms underlying the effects of S100A9.<bold>Results: </bold>S100A9 was upregulated in the lung tissues of LPS-treated mice. However, inhibition of S100A9 alleviated LPS-induced lung injury. Additionally, S100A9 blockade also attenuated the inflammatory responses and apoptosis in the lungs of LPS-challenged mice. Furthermore, the increased expression of NLRP3 was also suppressed by S100A9 blockade, while S100A9 blockade had no effect on NLRP3-/- mice. In vitro, S100A9 downregulation mitigated LPS-induced inflammation. Interestingly, these effects were blunted by NLRP3 overexpression.<bold>Conclusion: </bold>The results of the current study suggested that inhibition of S100A9 could protect against LPS-induced lung injury via inhibiting the NLRP3 pathway. Therefore, S100A9 blockade could be considered as a novel therapeutic strategy for lung injury in sepsis.
- Subjects
LUNG injuries; ENZYME-linked immunosorbent assay; WESTERN immunoblotting; LIPOPOLYSACCHARIDES; CALCIUM-binding proteins; ACUTE diseases; MICE; ANIMALS
- Publication
Respiratory Research, 2021, Vol 22, Issue 1, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/s12931-021-01641-y