title: Artesunate protects sepsis model mice challenged with Staphylococcus aureus by decreasing TNF-alpha release via inhibition TLR2 and Nod2 mRNA expressions and transcription factor NF-kappaB activation.
abstract: 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-kappaB 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-kappaB activation.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Xichun
authors.initials: X
authors.lastname: Pan
authors.forename: Guofu
authors.initials: G
authors.lastname: Ding
authors.forename: Hongwei
authors.initials: H
authors.lastname: Cao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Jiang
authors.forename: Jiang
authors.initials: J
authors.lastname: Zheng
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D007202:Indicators and Reagents; D007249:Inflammation / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis*; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications* / Q000473:pathology; D013203:Staphylococcal Infections / Q000150:complications* / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D037621:Artemisinins; D016207:Cytokines; D007202:Indicators and Reagents; D016328:NF-kappa B; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D000077332:Artesunate