Kim Han Geun, Lee Seung Yeon, Kim Na-Ra, Ko Mi Yeon, Lee Jung Min, Yi Tae-Hoo, Chung Sung Kyun, Chung Dae Kyun
Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin, Korea.
J Microbiol Biotechnol. 2008 Jun;18(6):1191-6.
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 aureus LTA (aLTA)-induced TNF-alpha production in THP- cells. Whereas pLTA scarcely induced TNF-alpha production, aLTA induced excessive TNF-alpha production. Interestingly, aLTA-induced TNF-alpha production was inhibited by pLTA pretreatment. Compared with pLTA, aLTA induced strong signal transduction through the MyD88, NF-kappaB, and MAP kinases. This signaling, however, was reduced by a pLTA pretreatment, and resulted in the inhibition of aLTA-induced TNF-alpha production. Whereas dealanylated LTAs, as well as native LTAs, contributed to TNF- induction or TNF-alpha 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.
金黄色葡萄球菌是革兰氏阳性败血症的常见病原体,其脂磷壁酸(LTA)可能在导致革兰氏阳性细菌性败血症休克中起重要作用。在此,我们证明从植物乳杆菌中分离出的高度纯化的LTA(pLTA)可抑制金黄色葡萄球菌LTA(aLTA)诱导的THP-细胞中TNF-α的产生。虽然pLTA几乎不诱导TNF-α的产生,但aLTA却诱导过量的TNF-α产生。有趣的是,pLTA预处理可抑制aLTA诱导的TNF-α产生。与pLTA相比,aLTA通过MyD88、NF-κB和丝裂原活化蛋白激酶诱导强烈的信号转导。然而,这种信号转导通过pLTA预处理而减弱,并导致aLTA诱导的TNF-α产生受到抑制。虽然去丙氨酰化的LTA以及天然LTA有助于TNF诱导或TNF-α减少,但去酰化的LTA则不然,这表明LTA的酰基链在LTA介导的免疫调节中起重要作用。这些结果表明,pLTA可能作为aLTA的拮抗剂,并且拮抗性pLTA可能是抑制革兰氏阳性细菌引起的败血症休克的有用药物。