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Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Protostemonine alleviates heat-killed methicillin-resistant Staphylococcus aureus-induced acute lung injury through
Yaxian Wu1, Yunjuan Nie1, Jianfeng Huang2
1Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, PR China.
Abstract:
Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) caused by gram-positive bacteria threatens human life because effective treatments and medicines is unavailable. Protostemonine (PSN), an active alkaloid mainly isolated from the roots of Stemona sesslifolia, has anti-inflammatory effects on asthma and gram-negative bacteria-induced ALI. Here, we found that PSN exhibits anti-inflammatory effects and alleviates heat-killed methicillin-resistant Staphylococcus aureus (HKMRSA)-induced pneumonia. PSN treatment significantly attenuated HKMRSA-induced pathological injury, pulmonary neutrophil infiltration, tissue permeability and the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in murine ALI model. In addition, PSN decreased the content of TNF-α, IL-1β, IL-6 and the expression of iNOS, as well as the production of NO in HKMRSA-induced bone marrow derived macrophages (BMDMs). Furthermore, treatment with PSN suppressed the activation of MAPKs (e.g. p38 MAPK, JNK and ERK) and NF-κB. Collectively, our results suggest that PSN ameliorates gram-positive bacteria-induced ALI in mice by inhibition of the MAPK and NF-κB signaling pathways, and our studies suggest that PSN might be a novel candidate for treating ALI/ARDS.
Insights
Protostemonine (PSN) reduces inflammation and lung injury caused by gram-positive bacteria. This study suggests PSN may be a promising new treatment for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).
Area of Science:
- Pharmacology
- Immunology
- Respiratory Medicine
Background:
- Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions with limited treatment options, especially when caused by gram-positive bacteria.
- Protostemonine (PSN), an alkaloid from Stemona sesslifolia, has demonstrated anti-inflammatory properties against certain conditions.
- Existing research indicates PSN's efficacy in models of asthma and gram-negative bacteria-induced ALI.
Purpose of the Study:
- To investigate the anti-inflammatory effects of Protostemonine (PSN) in a mouse model of pneumonia induced by heat-killed methicillin-resistant Staphylococcus aureus (HKMRSA).
- To evaluate PSN's potential as a therapeutic agent for gram-positive bacteria-induced ALI/ARDS.
Main Methods:
- Establishment of a murine model of ALI using HKMRSA.
- Administration of PSN to assess its impact on pathological injury, neutrophil infiltration, and cytokine production.
- Analysis of pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6) and nitric oxide (NO) production in lung tissue and bone marrow-derived macrophages (BMDMs).
- Investigation of the effects of PSN on MAPK and NF-κB signaling pathways.
Main Results:
- PSN treatment significantly reduced HKMRSA-induced pathological lung injury, neutrophil infiltration, and tissue permeability.
- PSN markedly decreased the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and NO in both the murine ALI model and HKMRSA-stimulated BMDMs.
- PSN effectively suppressed the activation of key inflammatory signaling pathways, including MAPKs (p38, JNK, ERK) and NF-κB.
Conclusions:
- Protostemonine ameliorates gram-positive bacteria-induced ALI in mice.
- The therapeutic effects of PSN are mediated through the inhibition of MAPK and NF-κB signaling pathways.
- PSN represents a potential novel therapeutic candidate for treating ALI and ARDS.
