Differential regulation of proinflammatory mediators following LPS- and ATP-induced activation of monocytes from patients with antiphospholipid syndrome.
Differential regulation of proinflammatory mediators following LPS- and ATP-induced activation of monocytes from patients with antiphospholipid syndrome.
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DOI：
10.1155/2015/292851
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发表时间：
2015
影响因子：
--
通讯作者：
Manukyan G
中科院分区：
文献类型：
--
作者：
Martirosyan A;Petrek M;Navratilova Z;Blbulyan A;Boyajyan A;Manukyan G
抗磷脂综合征（APS）是一种获得性自身免疫性疾病，其特征是与抗磷脂抗体存在相关的复发性血栓形成和妊娠发病率。越来越多的证据支持单核细胞参与APS发病机制。单核细胞的炎症激活促进血栓形成和其他APS并发症。然而，其激活的机制研究甚少。我们的目的是使用比较qRT-PCR确定单核细胞暴露于低浓度脂多糖（LPS）和LPS +三磷酸腺苷（ATP）后的转录活性。结果显示，LPS显著增加APS细胞中TLR 2、IL-23、CCL 2、CXCL 10、IL-1β和IL-6的转录水平，而在来自健康供体的细胞中，LPS导致IL-6和STAT 3 mRNA升高。细胞的双重刺激导致从健康供体分离的单核细胞中的NLRP 3和APS细胞中的CCL 2、IL-1β的mRNA水平降低。相反，在用LPS + ATP培养细胞后，两个研究组中的TLR 2 mRNA均升高。因此，研究结果表明APS细胞对LPS的敏感性增加，这可能有助于血栓形成并增强自身免疫过程的发展或进展。低浓度ATP可降低LPS诱导的APS单核细胞的炎症状态，这可能是其调节细胞炎症状态的一种潜在机制。
Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by recurrent thrombosis and pregnancy morbidity in association with the presence of antiphospholipid antibodies. Growing evidence supports the involvement of monocytes in APS pathogenesis. Inflammatory activation of monocytes promotes thrombus formation and other APS complications. However, mechanisms underlying their activation are poorly investigated. We aimed to determine transcriptional activity of monocytes after exposing them to low concentrations of lipopolysaccharide (LPS) and LPS + adenosine triphosphate (ATP) using comparative qRT-PCR. The results showed that LPS significantly increased transcriptional levels of TLR2, IL-23, CCL2, CXCL10, IL-1β, and IL-6 in APS cells, while, in cells from healthy donors, LPS resulted in IL-6 and STAT3 elevated mRNAs. Double stimulation of the cells resulted in decreased mRNA levels of NLRP3 in monocytes isolated from healthy donors and CCL2, IL-1β in APS cells. By contrast, TLR2 mRNAs were elevated in both investigated groups after culture of the cells with LPS + ATP. Thus, the findings indicate increased sensitivity of APS cells to LPS that may contribute to thrombus formation and enhance development or progression of autoimmune processes. Low concentrations of ATP diminish LPS-induced inflammatory state of APS monocytes which might be a potential mechanism which regulates inflammatory state of the cells.
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影响因子：
5.5
作者：
Laliberte, RE;Perregaux, DG;Gabel, CA
通讯作者：
Gabel, CA
DOI：
10.1126/science.1183021
发表时间：
2010-01-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iwasaki A;Medzhitov R
通讯作者：
Medzhitov R
影响因子：
6.7
作者：
Bodin, P;Burnstock, G
通讯作者：
Burnstock, G
DOI：
10.1016/s0002-9378(12)90915-1
发表时间：
1993-01-01
影响因子：
9.8
作者：
BRANCH, DW;RODGERS, GM
通讯作者：
RODGERS, GM
影响因子：
7.5
作者：
Kuwana, M
通讯作者：
Kuwana, M