A dipalmitoylated lipoprotein from Mycoplasma pneumoniae activates NF-κB through TLR1, TLR2, and TLR6
A dipalmitoylated lipoprotein from Mycoplasma pneumoniae activates NF-κB through TLR1, TLR2, and TLR6
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DOI：
10.4049/jimmunol.175.7.4641
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发表时间：
2005-10-01
影响因子：
4.4
通讯作者：
Kuwano, K
中科院分区：
文献类型：
--
作者：
Shimizu, T;Kida, Y;Kuwano, K
肺炎支原体感染的发病机制被认为部分归因于过度的免疫反应。最近，已报道来自支原体的脂蛋白诱导NF-κ B活化。在这项研究中，我们研究了M。pneumoniae激活NF-κ B，并鉴定了负责NF-κ B激活的活性组分。M.发现在人单核细胞系THP-1中通过TLR 2诱导NF-κ B。脂质相关膜蛋白的活性成分为F_0 F_1-ATP酶（F_0 F_1-ATP酶）的一个亚基B。假定F0 F1-ATP酶含有两个棕榈酸。F0 F1-ATP酶对NF-κ B的激活被TLR 1和TLR 6的显性负性结构抑制。这些结果表明，F（0）F（1-）ATP酶对NF-κ B B的激活依赖于TLR 1、TLR 2和TLR 6。脂蛋白脂酶预处理可降低F0 F1-ATP酶的活性，但蛋白酶不影响F0 F1-ATP酶的活性，提示F0 F1-ATP酶的脂质部分对NF-κ B B的活化起重要作用。因此，从M.发现肺炎链球菌通过TLR 1、TLR 2和TLR 6激活NF-κ B。
The pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributed to excessive immune responses. Recently, lipoproteins from mycoplasmas have been reported to induce NF-kappa B activation. In this study, we examined the ability of lipoproteins from M. pneumoniae to activate NF-kappa B, and the active component responsible for the NF-kappa B activation was identified. Lipid-associated membrane proteins from M. pneumoniae were found to induce NF-kappa B through TLR 2 in a human monocytic cell line, THP-1. The active component of the Lipid-associated membrane proteins was a subunit b of F0F1-type ATPase (F0F1-ATPase). The F0F1-ATPase is assumed to contain two palmitic acids. The activation of NF-kappa B by the F0F1-ATPase was inhibited by a dominant negative construct of TLR1 and TLR6. These results indicate that the activation of NF-kappa B by F(0)F(1-)ATPase is dependent on TLR1, TLR2, and TLR6. The activity of the F0F1-ATPase was decreased with pretreatment of lipoprotein lipase but not protease, indicating that the lipid moiety of the F0F1-ATPase was important for the NF-kappa B activation. Thus, a dipalmitoylated lipoprotein from M. pneumoniae was found to activate NF-kappa B through TLR1, TLR2, and TLR6.