Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety.
Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety.
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DOI：
10.1016/j.micinf.2008.07.029
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发表时间：
2008-10
影响因子：
5.8
通讯作者：
Pal U
中科院分区：
文献类型：
--
作者：
Yang X;Izadi H;Coleman AS;Wang P;Ma Y;Fikrig E;Anguita J;Pal U
伯氏疏螺旋体侵入哺乳动物关节导致莱姆关节炎的发生。除螺旋体脂质外，还存在蛋白抗原，其在关节中丰富并参与B。Burgdorferi诱导的宿主炎症反应，是未知的。在这里，我们报告的主要产品的B。在鼠和人关节中诱导的伯氏碱性膜蛋白（bmp）A/B操纵子具有炎性特性。与野生型B相比。bmpA/B突变体burgdorferi在培养的人滑膜细胞中诱导了显著较低水平的促炎细胞因子TNF-α和IL-1β，这可以使用bmpA/B互补突变体来恢复，并且更直接地，在添加重组BmpA后，而不是Bmp B或对照螺旋体蛋白。非脂化和脂化形式的BmpA诱导相似水平的细胞因子，并且不受脂多糖抑制剂多粘菌素B处理的影响。bmpA/B突变体在诱导滑膜细胞中NF-κB和p38 MAP激酶信号通路方面也受到损害，这些通路被非脂化的BmpA激活。这些结果表明，BmpA的蛋白质部分可以通过激活NF-κB和p38 MAP激酶途径诱导滑膜细胞中的细胞因子应答，因此，可能有助于莱姆关节炎的发生。
Borrelia burgdorferi invasion of mammalian joints results in genesis of Lyme arthritis. Other than spirochete lipids, existence of protein antigens, which are abundant in joints and participate in B. burgdorferi-induced host inflammatory response, is unknown. Here, we report that major products of the B. burgdorferi basic membrane protein (bmp) A/B operon that are induced in murine and human joints, possess inflammatory properties. Compared to the wild type B. burgdorferi, an isogenic bmpA/B mutant induced significantly lower levels of pro-inflammatory cytokines TNF-α and IL-1β in cultured human synovial cells, which could be restored using bmpA/B-complemented mutants, and more directly, upon addition of recombinant BmpA, but not BmpB or control spirochete proteins. Non-lipidated and lipidated versions of BmpA induced similar levels of cytokines, and remained unaffected by treatment with lipopolysaccharide inhibitor, polymyxin B. The bmpA/B mutant was also impaired in the induction of NF-κB and p38 MAP kinase signaling pathways in synovial cells, which were activated by non-lipidated BmpA. These results show that a protein moiety of BmpA can induce cytokine responses in synovial cells via activation of the NF-κB and p38 MAP kinase pathways and thus, could potentially contribute to the genesis of Lyme arthritis.
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DOI：
10.1084/jem.20070962
发表时间：
2008-01-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pal U;Wang P;Bao F;Yang X;Samanta S;Schoen R;Wormser GP;Schwartz I;Fikrig E
通讯作者：
Fikrig E
影响因子：
4.4
作者：
Behera, Aruna K.;Hildebrand, Ethan;Hu, Linden T.
通讯作者：
Hu, Linden T.
影响因子：
3.1
作者：
Moore, Meagan W.;Cruz, Adriana R.;Radolf, Justin D.
通讯作者：
Radolf, Justin D.
影响因子：
4.8
作者：
Kiss-Toth, E;Bagstaff, SM;Dower, SK
通讯作者：
Dower, SK
DOI：
10.1128/cdli.12.8.935-940.2005
发表时间：
2005-08-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Bryksin, AV;Godfrey, HP;Cabello, FC
通讯作者：
Cabello, FC