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Updated: Mar 27, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Silencing of Paralemmin-3 Protects Mice from lipopolysaccharide-induced acute lung injury
Shaoying Li1, Liang Guo2, Yunfeng Zhao3
1Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Department of Respiratory Medicine, Kunming General Hospital of Chengdu Military Command, Kunming, China.
Abstract:
Excessive inflammatory response induced by lipopolysaccharide (LPS) plays a critical role in the development of acute lung injury (ALI). Paralemmin-3 (PALM3) is a novel protein that can modulate LPS-stimulated inflammatory responses in alveolar epithelial A549 cells. However, it remains unclear whether it is involved in the progression of ALI in vivo. Therefore, we studied the role of PALM3 in the pathogenesis of ALI induced by LPS. ALI was induced by LPS peritoneal injection in C57BL/6J mice. Lentivirus-mediated small interfering RNA (siRNA) targeting the mouse PALM3 gene and a negative control siRNA were intranasally administered to the mice. We found that the expression of PALM3 was up-regulated in the lung tissues obtained from the mouse model of LPS-induced ALI. The LPS-evoked inflammatory response (neutrophils and the concentrations of proinflammatory cytokines [IL-6, IL-1β, TNF-α, MIP-2] in the bronchoalveolar lavage fluid [BALF]), histologic lung injury (lung injury score), permeability of the alveolar capillary barrier (lung wet/dry weight ratio and BALF protein concentration) and mortality rates were attenuated in the PALM3 siRNA-treated mice. These results indicate that PALM3 contributes to the development of ALI in mice challenged with LPS. Inhibiting PALM3 through the intranasal application of specific siRNA protected against LPS-induced ALI.
Insights
Paralemmin-3 (PALM3) protein exacerbates acute lung injury (ALI) in mice. Inhibiting PALM3 with siRNA reduced inflammation and lung damage, suggesting PALM3 as a therapeutic target for ALI.
Area of Science:
- Pulmonary Medicine
- Immunology
- Molecular Biology
Background:
- Acute lung injury (ALI) is a severe condition often triggered by excessive inflammatory responses.
- Lipopolysaccharide (LPS) is a key inducer of inflammation in ALI.
- The role of Paralemmin-3 (PALM3) in ALI pathogenesis in vivo is not well understood.
Purpose of the Study:
- To investigate the role of PALM3 in LPS-induced ALI in a mouse model.
- To determine if inhibiting PALM3 can mitigate ALI progression.
Main Methods:
- Established an LPS-induced ALI mouse model.
- Administered lentivirus-mediated small interfering RNA (siRNA) targeting PALM3 intranasally.
- Assessed inflammatory markers, lung injury scores, alveolar-capillary barrier permeability, and mortality rates.
Main Results:
- PALM3 expression was elevated in LPS-induced ALI mouse lungs.
- PALM3 siRNA treatment significantly reduced inflammatory cell infiltration and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF).
- Inhibition of PALM3 attenuated lung injury, decreased lung wet/dry weight ratio and BALF protein concentration, and improved survival rates.
Conclusions:
- PALM3 plays a significant role in the development of LPS-induced ALI.
- Intranasal administration of PALM3-specific siRNA offers a protective effect against ALI.
- Targeting PALM3 presents a potential therapeutic strategy for ALI.
