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-kappa B pathways account for the anti-inflammatory role of MCL after PGN stimulation. MCL reduced IL-6 secretion through down-regulating NF-kappa B 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-alpha, MCP-1/CCL2 and IFN-gamma 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).
[1]Shanghai Univ Tradit Chinese Med, Dept Immunol & Microbiol, Shanghai 201203, Peoples R China.
[2]Shaanxi Univ Chinese Med, Sch Clin Med, Taiyuan 712046, Peoples R China.
[3]Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Med, MRC Human Immunol Unit, Oxford OX3 9DS, England.
[4]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Respirat, Shanghai 200032, Peoples R China.
[5]Shanghai Univ Tradit Chinese Med, Longhua Hosp, CcCRDD, Inst Digest Dis, Shanghai 200032, Peoples R China.
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