Related Experiment Video
Updated: Oct 6, 2025
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Methionine Restriction Prevents Lipopolysaccharide-Induced Acute Lung Injury via Modulating CSE/H2S Pathway
Jiaxiang Duan1, Lunli Xiang2, Zhen Yang1
1Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Abstract:
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) result in high mortality, whereas effective treatments are limited. Methionine restriction (MR) has been reported to offer various benefits against multiple pathological processes of organ injuries. However, it remains unknown whether MR has any potential therapeutic value for ALI/ARDS. The current study was set to investigate the therapeutic potential of MR on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms. We found that MR attenuated LPS-induced pulmonary edema, hemorrhage, atelectasis, and alveolar epithelial cell injuries in mice. MR upregulated cystathionine-gamma-lyase (CSE) expression and enhanced the production of hydrogen sulfide (H2S). MR also inhibited the activation of Toll-like receptors 4 (TLR4)/NF-κB/NOD-like receptor protein 3 (NLRP3), then reduced IL-1β, IL-6, and TNF-α release and immune cell infiltration. Moreover, the protective effects of MR on LPS-induced ALI were abrogated by inhibiting CSE, whereas exogenous H2S treatment alone mimicked the protective effects of MR in Cse-/- mice after LPS administration. In conclusion, our findings showed that MR attenuated LPS-induced lung injury through CSE and H2S modulation. This work suggests that developing MR towards clinical use for ALI/ARDS patients may be a valuable strategy.
Insights
Methionine restriction (MR) shows therapeutic potential for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This study found MR protects against lung injury by modulating cystathionine-gamma-lyase (CSE) and hydrogen sulfide (H2S) pathways.
Area of Science:
- Respirology
- Biochemistry
- Pathology
Background:
- Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions with limited effective treatments.
- Methionine restriction (MR) has demonstrated protective effects in various organ injury models.
- The therapeutic potential of MR for ALI/ARDS remains unexplored.
Purpose of the Study:
- To investigate the therapeutic efficacy of methionine restriction (MR) in a mouse model of lipopolysaccharide (LPS)-induced ALI.
- To elucidate the underlying molecular mechanisms of MR's protective effects in ALI.
Main Methods:
- Induction of ALI in mice using lipopolysaccharide (LPS).
- Administration of methionine restriction (MR) and assessment of lung injury markers.
- Measurement of cystathionine-gamma-lyase (CSE) expression and hydrogen sulfide (H2S) production.
- Analysis of Toll-like receptor 4 (TLR4)/NF-κB/NOD-like receptor protein 3 (NLRP3) pathway activation and inflammatory cytokine release.
- Pharmacological inhibition of CSE and administration of exogenous H2S in relevant mouse models.
Main Results:
- MR significantly attenuated LPS-induced pulmonary edema, hemorrhage, atelectasis, and alveolar epithelial cell injury.
- MR upregulated CSE expression and enhanced H2S production.
- MR inhibited TLR4/NF-κB/NLRP3 pathway activation, reducing pro-inflammatory cytokine release (IL-1β, IL-6, TNF-α) and immune cell infiltration.
- Inhibition of CSE abolished MR's protective effects, while exogenous H2S mimicked MR's benefits in CSE-deficient mice.
Conclusions:
- Methionine restriction alleviates LPS-induced lung injury in mice.
- The protective effects are mediated through the upregulation of CSE and subsequent enhancement of H2S production.
- MR inhibits the TLR4/NF-κB/NLRP3 inflammatory pathway.
- MR represents a potential therapeutic strategy for ALI/ARDS.
