Lysophosphatidylcholine triggers TLR2- and TLR4-mediated signaling pathways but counteracts LPS-induced NO synthesis in peritoneal macrophages by inhibiting NF-κB translocation and MAPK/ERK phosphorylation.
Lysophosphatidylcholine triggers TLR2- and TLR4-mediated signaling pathways but counteracts LPS-induced NO synthesis in peritoneal macrophages by inhibiting NF-κB translocation and MAPK/ERK phosphorylation.
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DOI：
10.1371/journal.pone.0076233
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Silva-Neto MA
中科院分区：
文献类型：
--
作者：
Carneiro AB;Iaciura BM;Nohara LL;Lopes CD;Veas EM;Mariano VS;Bozza PT;Lopes UG;Atella GC;Almeida IC;Silva-Neto MA
溶血磷脂酰胆碱（LPC）是氧化低密度脂蛋白（oxLDL）的主要磷脂成分，通常被认为是几种人类疾病的标志物，如动脉粥样硬化，癌症和糖尿病。一些研究表明oxLDL调节Toll样受体（TLR）信号传导。然而，存在于oxLDL颗粒中并可触发TLR信号传导的效应分子尚不清楚。LPC以前被描述为脓毒症的衰减剂和免疫抑制剂。在本研究中，我们评估了LPC作为TLR介导的信号通路的双重调节剂的作用。用TLR表达构建体转染HEK 293 A细胞，并用具有不同脂肪酸链长度和饱和水平的LPC分子刺激。通过NF-κ B B活化和IL-8产生评估，所有LPC分子均活化TLR 4和TLR 2 -1信号传导。这些数据通过小鼠腹腔巨噬细胞分离核中NF-κ B B易位的Western印迹分析得到证实。而LPC则能抑制LPS诱导的TLR 4信号转导。在这种情况下，NF-κ B B易位、一氧化氮（NO）合成和诱导型一氧化氮合酶（iNOS）的表达被阻断。此外，LPC激活小鼠巨噬细胞中的MAP激酶p38和JNK，但不激活ERK。有趣的是，LPC阻断LPS诱导的ERK激活的腹腔巨噬细胞，但不是在TLR转染的细胞。上述结果表明LPC是一种具有双重活性的配体分子。它能够通过激活TLR 4-和TLR 2 -1-介导的信号传导来触发经典的促炎表型。然而，在经典TLR配体的存在下，LPC抵消了TLR介导的细胞内反应，最终诱导抗炎表型; LPC因此可能在细胞免疫反应和疾病进展的调节中发挥作用。
Lysophosphatidylcholine (LPC) is the main phospholipid component of oxidized low-density lipoprotein (oxLDL) and is usually noted as a marker of several human diseases, such as atherosclerosis, cancer and diabetes. Some studies suggest that oxLDL modulates Toll-like receptor (TLR) signaling. However, effector molecules that are present in oxLDL particles and can trigger TLR signaling are not yet clear. LPC was previously described as an attenuator of sepsis and as an immune suppressor. In the present study, we have evaluated the role of LPC as a dual modulator of the TLR-mediated signaling pathway. HEK 293A cells were transfected with TLR expression constructs and stimulated with LPC molecules with different fatty acid chain lengths and saturation levels. All LPC molecules activated both TLR4 and TLR2-1 signaling, as evaluated by NF-қB activation and IL-8 production. These data were confirmed by Western blot analysis of NF-қB translocation in isolated nuclei of peritoneal murine macrophages. However, LPC counteracted the TLR4 signaling induced by LPS. In this case, NF-қB translocation, nitric oxide (NO) synthesis and the expression of inducible nitric oxide synthase (iNOS) were blocked. Moreover, LPC activated the MAP Kinases p38 and JNK, but not ERK, in murine macrophages. Interestingly, LPC blocked LPS-induced ERK activation in peritoneal macrophages but not in TLR-transfected cells. The above results indicate that LPC is a dual-activity ligand molecule. It is able to trigger a classical proinflammatory phenotype by activating TLR4- and TLR2-1-mediated signaling. However, in the presence of classical TLR ligands, LPC counteracts some of the TLR-mediated intracellular responses, ultimately inducing an anti-inflammatory phenotype; LPC may thus play a role in the regulation of cell immune responses and disease progression.
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影响因子：
5.1
作者：
Bzowska, Malgorzata;Nogiec, Anna;Skrzeczynska-Moncznik, Joanna;Mickowska, Barbara;Guzik, Krzysztof;Pryjma, Juliusz
通讯作者：
Pryjma, Juliusz
影响因子：
6.4
作者：
Magalhaes, Kelly G.;Almeida, Patricia E.;Bozza, Patricia T.
通讯作者：
Bozza, Patricia T.
DOI：
10.1164/ajrccm/142.1.157
发表时间：
1990-07-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
MEHTA, D;GUPTA, S;AGRAWAL, KP
通讯作者：
AGRAWAL, KP
影响因子：
2.9
作者：
Miller, Ingrid;Radwan, Marta;Gemeiner, Manfred
通讯作者：
Gemeiner, Manfred
影响因子：
4.3
作者：
Aiyar, Nambi;Disa, Jyoti;Douglas, Stephen A.
通讯作者：
Douglas, Stephen A.