Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 10, Issue 3, Pages 344-350Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2009.12.006
Keywords
Sepsis; Artesunate; Staphylococcus aureus; Peptidoglycan; TNF-alpha; TLR2; Nod2; NF-kappa B
Categories
Funding
- National Natural Science Foundation of China [30772628]
- Tackle Key Problems in Science and Technology of Chongqing, China [9398]
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Gram-positive bacteria have become the most common Organisms responsible for the development of sepsis. Staphylococcus aureus (S. aureus) is the major gram-positive pathogen in both community-acquired and nosocomial infections. The Mortality associated with nosocomial infections caused by S. aureus may vary but are generally high. In the present study, we found that artesunate (AS) could protect mice against a lethal challenge with heat-killed S. aureus in a dose-dependent manner. and AS in combination with ampicillin sodium-sulbactam sodium (AMPS) Could further increase survival of mice challenged with live S. aureus; than AMPS alone. This protection was associated with reductions of serum at TNF-alpha. level. In in vitro experiments, AS-pretreatment strongly inhibited TNF-alpha release from murine peritoneal macrophage induced by heat-killed S. aureus or peptidoglycan in a dose-dependent manner. AS reduced the Toll like receptor 2 (TLR2) and nucleotide-binding oligomerization domain containing 2 (Nod2) mRNA expressions up-regulated by heat-killed S. aureus and inhibited NF-kappa B activation induced by heat-killed S. aureus. In conclusion, our results demonstrated that AS-mediated protection on septic mice challenged with S. aureus was associated with its reduction on TNF-alpha release via inhibition of TLR2 and Nod2 mRNA expressions and transcription factor NF-kappa B activation. (C) 2009 Published by Elsevier B.V.
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