Borrelia burgdorferi basic membrane protein A initiates proinflammatory chemokine storm in THP 1-derived macrophages via the receptors TLR1 and TLR2.
Borrelia burgdorferi basic membrane protein A initiates proinflammatory chemokine storm in THP 1-derived macrophages via the receptors TLR1 and TLR2.
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伯氏疏螺旋体碱性膜蛋白 A 通过受体 TLR1 和 TLR2 在 THP 1 衍生的巨噬细胞中引发促炎趋化因子风暴
DOI：
10.1016/j.biopha.2019.108874
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发表时间：
2019-07
影响因子：
7.5
通讯作者：
Lvyan Tao
中科院分区：
文献类型：
--
作者：
Hua Zhao;Xiting Dai;Xinlin Hai;Aihua Liu;Fukai Bao;Ruolan Bai;Zhenhua Ji;Miaomiao Jian;Zhe Ding;ME Abi;Taigui Chen;Lisha Luo;Mingbiao Ma;Lvyan Tao
莱姆病，又称莱姆疏螺旋体病，是由伯氏疏螺旋体引起的人畜共患病。莱姆关节炎是莱姆病晚期最常见、最严重、危害最大的表现，与伯氏疏螺旋体碱性膜蛋白A(BMPA)密切相关。据报道，趋化因子在莱姆关节炎中也起着重要作用。Toll样受体识别并结合在微生物中结构保守的病原体相关分子，激活转录事件，包括细胞因子的产生、炎症和组织损伤。我们推测BMPA可通过TLRs及其下游分子诱导致炎趋化因子风暴，TLR1、TLR2、TLR5、TLR6和接头蛋白MyD88可能参与了这一过程。我们利用人类单核细胞白血病细胞系THP-1和重组BMPA(RBmpA)探索了这一假设。细胞表面TLR1和TLR2在用rBmpA刺激之前用特异性抗体中和，并用趋化因子芯片分析趋化因子的分泌。进一步分析rBmpA刺激后4种TLRs和MyD88的表达水平。用rBmpA刺激后，7种细胞因子水平升高。此外，TLR1和TLR2抗体处理的细胞显示rBmpA诱导的趋化因子表达总体上减少。经rBmpA刺激后，TLR1、TLR2和MyD88的表达水平(mRNA和蛋白)均增加。我们的数据证实TLR1、TLR2和MyD88参与了BMPA诱导的促炎趋化因子，这可能与莱姆关节炎的发病密切相关。
Lyme disease, reffered to as Lyme borreliosis, is a tick-borne zoonotic disease caused byBorrelia burgdorferispirochetes. Lyme arthritis, the most common, serious and harmful manifestation during the late stages of Lyme disease, is closely associated with theBorrelia burgdorferibasic membrane protein A (BmpA). Chemokines are also reported to have an important role in Lyme arthritis. Toll-like receptors (TLRs) recognize and bind to pathogen-associated molecules which are structurally conserved among microbes, to activate transcriptional events, including cytokine production, inflammation, and tissue damage. We speculated that BmpA could induce a storm of proinflammatory chemokines via TLRs and downstream moleculars, and that TLR1, TLR2, TLR5, TLR6 and the adaptor protein, MyD88, may be involved in this process. We explored this hypothesis using the human monocytic leukemia cell line, THP-1, and recombinant BmpA (rBmpA). Cell surface TLR1 and TLR2 were neutralized using specific antibodies before stimulation with rBmpA and analysis of chemokine secretion using a chemokine chip. Further, the expressions level of the four TLRs and MyD88 were analyzed following stimulation with rBmpA. Stimulation with rBmpA resulted in elevated levels of seven cytokines. Further, TLR1 and TLR2 antibody treated cells exhibited an overall reduction in rBmpA-induced chemokine expression. TLR1, TLR2, and MyD88 expression levels (both mRNA and protein) increased after stimulation with rBmpA. Our data confirm that TLR1, TLR2, and MyD88 are involved in BmpA-induced proinflammatory chemokines, which may be closely involved in Lyme arthritis pathogenesis.
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影响因子：
4.9
作者：
Shin JJ;Strle K;Glickstein LJ;Luster AD;Steere AC
通讯作者：
Steere AC
DOI：
10.20506/rst.23.2.1503
发表时间：
2004-08
期刊：
Revue scientifique et technique
影响因子：
--
作者：
R. Higgins
通讯作者：
R. Higgins
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
DOI：
--
发表时间：
2000-08
期刊：
Journal of the Egyptian Society of Parasitology
影响因子：
--
作者：
N. Helmy
通讯作者：
N. Helmy
影响因子：
5.8
作者：
Yang X;Izadi H;Coleman AS;Wang P;Ma Y;Fikrig E;Anguita J;Pal U
通讯作者：
Pal U