The silencing of SAAL1 suppresses pneumonia progression via modulating the NLR signaling pathway.

Background: Pneumonia is a severe respiratory disease in both children and elderly people and is commonly accompanied with inflammation and lung injury. In this study, we sought to examine the expression and function of serum amyloid A-like 1 (SAAL1) in a lipopolysaccharide (LPS)-stimulated pneumonia model. Methods: An LPS-stimulated mouse model and A549 lung cell model were established to examine the effects of SAAL1 in pneumonia. The expression of SAAL1 in pneumonia was analyzed in a Gene Expression Omnibus (GEO) data set and the established mouse model. Lung injury, edema, neutrophil infiltration, and the production of inflammatory factors were measured by histological analysis and enzyme-linked immunosorbent assays (ELISAs). A Gene Set Enrichment Analysis (GSEA) was performed to analyze the SAAL1-related pathways. The viability and apoptosis of A549 cells upon LPS stimulation and the knockdown of SAAL1 were checked by cell counting kit 8 (CCK-8) and flow cytometry. Results: The level of SAAL1 was significantly elevated in the lung tissues from the LPS-stimulated mice. Treatment with SAAL1 depletion alleviated the lung injury, edema, and neutrophil infiltration. The LPS-stimulated production of inflammatory factors, including tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6, were suppressed by the SAAL1 knockdown. The LPS treatment activated the NLR signaling pathway, and the depletion of SAAL1 suppressed this activation. The silencing of SAAL1 improved the viability and suppressed apoptosis in the LPS-stimulated A549 cells, while the overexpression of NLRP3 abolished the effects of SAAL1. Conclusions: The SAAL1 knockdown ameliorated LPS-induced lung injury and the inflammatory response by suppressing the NLR signaling pathway.