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Staphylococcus aureus is a common etiologic agent for Gram-positive sepsis, and its lipoteichoic acid (LTA) may be important in causing Gram-positive bacterial septic shock. Here, we demonstrate that highly purified LTA (pLTA) isolated from Lactobacillus plantarum inhibited S. aureus LTA (aLTA)-induced TNF-α production in THP-1 cells. Whereas pLTA scarcely induced TNF-α production, aLTA induced excessive TNF-α production. Interestingly, aLTA-induced TNF-α production was inhibited by pLTA pretreatment. Compared with pLTA, aLTA induced a strong signal transduction through the MyD88, NF-κB, and MAP kinases. This signaling, however, was reduced by a pLTA pretreatment, and resulted in the inhibition of aLTA-induced TNF-α production. Whereas dealanylated LTAs, as well as native LTAs, contributed to TNF-α induction or TNF-α reduction, deacylated LTAs did not, indicating that the acyl chain of LTA played an important role in the LTA-mediated immune regulation. These results suggest that pLTA may act as an antagonist for aLTA, and that an antagonistic pLTA may be a useful agent for suppressing the septic shock caused by Gram-positive bacteria.

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