Artesunate protects sepsis model mice challenged with Staphylococcus aureus by decreasing TNF-α release via inhibition TLR2 and Nod2 mRNA expressions and transcription factor NF-κB activation

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• 作者：Bin Li ; Jun Li ; Xichun Pan ; Guofu Ding ; Hongwei Cao ; Weiwei Jiang ; Jiang Zheng ; Hong Zhou
• 关键词：Sepsis ; Artesunate ; Staphylococcus aureus ; Peptidoglycan ; TNF-α ; TLR2 ; Nod2 ; NF-κ ; B
• 刊名：International Immunopharmacology
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：10
• 期：3
• 页码：344-350
• 全文大小：354 K

文摘

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-α level. In in vitro experiments, AS-pretreatment strongly inhibited TNF-α 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-κB 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-α release via inhibition of TLR2 and Nod2 mRNA expressions and transcription factor NF-κB activation.