Micheliolide provides protection of mice against Staphylococcus aureus and MRSA infection by down-regulating inflammatory response.
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).
Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Xinru
X
Jiang
Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Yuli
Y
Wang
School of Clinical Medicine, Shaanxi University of Chinese Medicine, Xi xian New District, Shaanxi 712046, China.
Yifei
Y
Qin
Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Weigang
W
He
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
Adel
A
Benlahrech
Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Qingwen
Q
Zhang
Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Xin
X
Jiang
Department of Respiration, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Zhenhui
Z
Lu
Institute of Digestive Diseases, China-Canada Center of Research for Digestive Diseases (ccCRDD), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Guang
G
Ji
Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.|MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
Yuejuan
Y
Zheng
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D045789:Sesquiterpenes, Guaiane / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D045789:Sesquiterpenes, Guaiane; C577928:micheliolide