S100A9 blockade prevents lipopolysaccharide-induced lung injury via suppressing the NLRP3 pathway.
Respir Res
; 22(1): 45, 2021 Feb 06.
Article
in English
| MEDLINE | ID: covidwho-1068592
ABSTRACT
BACKGROUND:
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.METHODS:
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 enzymelinked immunosorbent assay (ELISA), respectively. Furthermore, western blot analysis and RT-qPCR were carried out to investigate the molecular mechanisms underlying the effects of S100A9.RESULTS:
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.CONCLUSION:
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Lipopolysaccharides
/
Calgranulin B
/
Acute Lung Injury
/
NLR Family, Pyrin Domain-Containing 3 Protein
Type of study:
Experimental Studies
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Respir Res
Year:
2021
Document Type:
Article
Affiliation country:
S12931-021-01641-y
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