PMID:22431984

Citation	Schaefers, MM, Breshears, LM, Anderson, MJ, Lin, YC, Grill, AE, Panyam, J, Southern, PJ, Schlievert, PM and Peterson, ML (2012) Epithelial proinflammatory response and curcumin-mediated protection from staphylococcal toxic shock syndrome toxin-1. PLoS ONE 7:e32813
Abstract	Staphylococcus aureus initiates infections and produces virulence factors, including superantigens (SAgs), at mucosal surfaces. The SAg, Toxic Shock Syndrome Toxin-1 (TSST-1) induces cytokine secretion from epithelial cells, antigen presenting cells (APCs) and T lymphocytes, and causes toxic shock syndrome (TSS). This study investigated the mechanism of TSST-1-induced secretion of proinflammatory cytokines from human vaginal epithelial cells (HVECs) and determined if curcumin, an anti-inflammatory agent, could reduce TSST-1-mediated pathology in a rabbit vaginal model of TSS. TSST-1 caused a significant increase in NF-κB-dependent transcription in HVECs that was associated with increased expression of TNF- α, MIP-3α, IL-6 and IL-8. Curcumin, an antagonist of NF-κB-dependent transcription, inhibited IL-8 production from ex vivo porcine vaginal explants at nontoxic doses. In a rabbit model of TSS, co-administration of curcumin with TSST-1 intravaginally reduced lethality by 60% relative to 100% lethality in rabbits receiving TSST-1 alone. In addition, TNF-α was undetectable from serum or vaginal tissue of curcumin treated rabbits that survived. These data suggest that the inflammatory response induced at the mucosal surface by TSST-1 is NF-κB dependent. In addition, the ability of curcumin to prevent TSS in vivo by co-administration with TSST-1 intravaginally suggests that the vaginal mucosal proinflammatory response to TSST-1 is important in the progression of mTSS.
Links	PubMed PMC3303796 Online version:10.1371/journal.pone.0032813
Keywords	Animals; Bacterial Toxins/toxicity; Cell Line, Transformed; Chemokines/metabolism; Curcumin/pharmacology; Curcumin/therapeutic use; Disease Models, Animal; Enterotoxins/toxicity; Epithelial Cells/drug effects; Epithelial Cells/microbiology; Epithelial Cells/pathology; Female; Humans; Inflammation Mediators/metabolism; Interleukin-8/biosynthesis; Mucous Membrane/drug effects; Mucous Membrane/microbiology; Mucous Membrane/pathology; NF-kappa B/metabolism; Protective Agents/pharmacology; Protective Agents/therapeutic use; Rabbits; Shock, Septic/drug therapy; Shock, Septic/immunology; Shock, Septic/microbiology; Shock, Septic/prevention & control; Signal Transduction/drug effects; Staphylococcus aureus/drug effects; Staphylococcus aureus/physiology; Superantigens/toxicity; Sus scrofa; Vagina/drug effects; Vagina/microbiology; Vagina/pathology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
STAAU:TSST		GO:0009405: pathogenesis	ECO:0000314:		P		Figure 1.	complete CACAO 4625
STAAU:TSST	involved_in	GO:0009405: pathogenesis	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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