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Evaluation of Antimicrobial Activities of Nanoparticles and Nanostructured Surfaces In Vitro
Published on: April 21, 2023
Micheliolide provides protection of mice against Staphylococcus aureus and MRSA infection by down-regulating
Xinru Jiang1, Yuli Wang1, Yifei Qin2
1Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Abstract:
A major obstacle to therapy in intensive care units is sepsis caused by severe infection. In recent years gram-positive (G+) bacteria, most commonly staphylococci, are thought to be the main pathogens. Micheliolide (MCL) was demonstrated to provide a therapeutic role in rheumatoid arthritis, inflammatory intestinal disease, colitis-associated cancer, and lipopolysaccharide (LPS, the main component of G- bacterial cell wall) induced septic shock. We proved here that MCL played an anti-inflammatory role in Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) induced peritonitis. It inhibited the expression of inflammatory cytokines and chemokines in macrophages and dendritic cells upon stimulation with peptidoglycan (PGN, the main cell wall composition of G+ bacteria). PI3K/Akt and NF-κB pathways account for the anti-inflammatory role of MCL after PGN stimulation. MCL reduced IL-6 secretion through down-regulating NF-κB activation and improved the survival status in mice challenged with a lethal dose of S. aureus. In MRSA infection mouse model, MCL down-regulated the expression of IL-6, TNF-α, MCP-1/CCL2 and IFN-γ in sera, and ameliorated the organ damage of liver and kidney. In conclusion, MCL can help maintain immune equilibrium and decrease PGN, S. aureus and MRSA-triggered inflammatory response. These provide the rationality for the potential usage of MCL in sepsis caused by G+ bacteria (e.g., S. aureus) and antibiotic-resistant bacteria (e.g., MRSA).
Insights
Micheliolide (MCL) reduces inflammation from gram-positive bacterial infections like Staphylococcus aureus. This compound helps improve survival rates and mitigate organ damage in sepsis models, offering potential therapeutic benefits.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Sepsis, a life-threatening condition often caused by severe infections, poses a significant therapeutic challenge in intensive care units.
- Gram-positive bacteria, particularly staphylococci, are increasingly recognized as primary pathogens in sepsis.
- Micheliolide (MCL) has shown therapeutic potential in various inflammatory conditions and lipopolysaccharide (LPS)-induced septic shock.
Purpose of the Study:
- To investigate the anti-inflammatory effects of Micheliolide (MCL) in models of Gram-positive bacterial peritonitis.
- To elucidate the molecular pathways involved in MCL's anti-inflammatory action against peptidoglycan (PGN) stimulation.
- To evaluate MCL's efficacy in improving survival and reducing organ damage in mouse models of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) infection.
Main Methods:
- Assessing the expression of inflammatory cytokines and chemokines in macrophages and dendritic cells stimulated with peptidoglycan (PGN).
- Analyzing the involvement of PI3K/Akt and NF-κB signaling pathways in MCL's anti-inflammatory response.
- Evaluating survival rates and organ damage (liver, kidney) in mouse models challenged with lethal doses of S. aureus and MRSA.
Main Results:
- MCL inhibited the expression of inflammatory cytokines and chemokines induced by PGN in immune cells.
- MCL's anti-inflammatory effects were mediated through the down-regulation of PI3K/Akt and NF-κB pathways.
- MCL treatment improved survival in mice infected with S. aureus and reduced inflammatory markers (IL-6, TNF-α, MCP-1/CCL2, IFN-γ) and organ damage in MRSA infection models.
Conclusions:
- Micheliolide (MCL) demonstrates significant anti-inflammatory properties against Gram-positive bacterial components like PGN.
- MCL effectively mitigates inflammatory responses and improves outcomes in experimental models of S. aureus and MRSA infections.
- These findings support the potential therapeutic application of MCL for sepsis caused by Gram-positive and antibiotic-resistant bacteria.
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