ATX and LPA receptor 3 are coordinately up‐regulated in lipopolysaccharide‐stimulated THP‐1 cells through PKR and SPK1‐mediated pathways

Song, Li; Xiong, Cong; Zhang, Junjie

doi:10.1016/j.febslet.2012.01.044

Cited by 13 publications

(18 citation statements)

References 18 publications

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“…While not examined in the current study, the various transcription pathways induced in monocytes for the production of ATX in the presence of LPS are likely to be similar in microglia [Li and Zhang, ; Li et al, ]. Microglia, as well as, monocytes/macrophages express TLR4 and CD14, the receptor and co‐receptor for LPS recognition.…”

Section: Discussionmentioning

confidence: 99%

“…Over expression of ATX in microglia improves their resistance to hydrogen peroxide, decreases intracellular reactive oxygen species and increases enzyme involved in the detoxification such as catalase demonstrating that ATX have a protective role in oxidative stress [Awada et al, ]. A role for ATX in the regulation of the acute inflammatory response has been previously proposed [Li and Zhang, ; Li et al, ]. In vivo studies reported a significant decrease in LPS‐induced plasma TNFα levels in mice pre‐treated with LPA while IL‐6 was not changed [Fan et al, ].…”

Section: Discussionmentioning

confidence: 99%

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Autotaxin Downregulates LPS‐Induced Microglia Activation and Pro‐Inflammatory Cytokines Production

Awada¹,

Saulnier-Blache

Grès

et al. 2014

J of Cellular Biochemistry

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Inflammation is essential in defense against infection or injury. It is tightly regulated, as over-response can be detrimental, especially in immune-privileged organs such as the central nervous system (CNS). Microglia constitutes the major source of inflammatory factors, but are also involved in the regulation of the inflammation and in the reparation. Autotaxin (ATX), a phospholipase D, converts lysophosphatidylcholine into lysophosphatidic acid (LPA) and is upregulated in several CNS injuries. LPA, a pleiotropic immunomodulatory factor, can induce multiple cellular processes including morphological changes, proliferation, death and survival. We investigated ATX effects on microglia inflammatory response to lipopolysaccharide (LPS), mimicking gram-negative infection. Murine BV-2 microglia and stable transfected, overexpressing ATX-BV-2 (A+) microglia were treated with LPS. Tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-10 mRNA and proteins levels were examined by qRT-PCR and ELISA, respectively. Secreted LPA was quantified by a radioenzymatic assay and microglial activation markers (CD11b, CD14, B7.1 and B7.2) were determined by flow cytometry. ATX expression and LPA production were significantly enhanced in LPS treated BV-2 cells. LPS induction of mRNA and protein level for TNFα and IL-6 were inhibited in A+ cells, while IL-10 was increased. CD11b, CD14, and B7.1 and B7.2 expressions were reduced in A+ cells. Our results strongly suggest deactivation of microglia and an IL-10 inhibitory of ATX with LPS induced microglia activation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Autotaxin Downregulates LPS‐Induced Microglia Activation and Pro‐Inflammatory Cytokines Production

Awada¹,

Saulnier-Blache

Grès

et al. 2014

J of Cellular Biochemistry

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“…Inhibition of LPA 1 partly blocked LPS-induced signaling and IL-6 release in lung epithelial cells [16]. In addition, in THP-1 cells, either downregulation of lysoPLD or LPA 3 attenuated LPS-induced CCL8 release [64]. These studies suggest that LPA receptors are involved in LPS signaling.…”

Section: Lpa Receptors In Murine Models Of Pulmonary Inflammatory mentioning

confidence: 99%

Lysophosphatidic acid (LPA) and its receptors: Role in airway inflammation and remodeling

Zhao

Natarajan

2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Lysophosphatidic acid (LPA), a simple bioactive phospholipid, is present in biological fluids such as plasma and bronchoalveolar lavage (BAL). It appears to have both pro- and anti-inflammatory roles in inflammatory lung diseases. Exogenous LPA promotes inflammatory responses by regulating the expression of chemokines, cytokines, and cytokine receptors in lung epithelial cells. In addition to the modulation of inflammatory responses, LPA regulates cytoskeleton rearrangement and confers protection against lung injury by enhancing lung epithelial cell barrier integrity and remodeling. The biological effects of LPA are mediated through its cell surface G-protein coupled LPA1-7 receptors. The roles of LPA receptors in lung fibrosis, asthma, and acute lung injury have been investigated using genetically engineered LPA receptor deficient mice and there appears to be a definitive role for endogenous LPA and its receptors in the pathogenesis of pulmonary inflammatory diseases. This review summarizes recent reports on the role of LPA and its receptors in the regulation of lung epithelial inflammatory responses and remodeling.

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“…The pro-atherosclerotic effects of LPA have been mainly tied to LPA 1 and LPA 3, which were reported to increase atherosclerosis development in apoE −/− mice27. Receptors LPA 1 and LPA 3 are widely expressed by immune cells2829, as well as endothelial30 and vascular smooth muscle cells31, with LPA 3 activation being involved in cell migration32 while LPA 1 shows both migratory33 and apoptotic effects34.…”

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confidence: 99%

Inhibition of lysophosphatidic acid receptors 1 and 3 attenuates atherosclerosis development in LDL-receptor deficient mice

Kritikou

Puijvelde

Heijden

et al. 2016

Sci Rep

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Lysophosphatidic acid (LPA) is a natural lysophospholipid present at high concentrations within lipid-rich atherosclerotic plaques. Upon local accumulation in the damaged vessels, LPA can act as a potent activator for various types of immune cells through its specific membrane receptors LPA1/3. LPA elicits chemotactic, pro-inflammatory and apoptotic effects that lead to atherosclerotic plaque progression. In this study we aimed to inhibit LPA signaling by means of LPA1/3 antagonism using the small molecule Ki16425. We show that LPA1/3 inhibition significantly impaired atherosclerosis progression. Treatment with Ki16425 also resulted in reduced CCL2 production and secretion, which led to less monocyte and neutrophil infiltration. Furthermore, we provide evidence that LPA1/3 blockade enhanced the percentage of non-inflammatory, Ly6Clow monocytes and CD4+ CD25+ FoxP3+ T-regulatory cells. Finally, we demonstrate that LPA1/3 antagonism mildly reduced plasma LDL cholesterol levels. Therefore, pharmacological inhibition of LPA1/3 receptors may prove a promising approach to diminish atherosclerosis development.

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ATX and LPA receptor 3 are coordinately up‐regulated in lipopolysaccharide‐stimulated THP‐1 cells through PKR and SPK1‐mediated pathways

Cited by 13 publications

References 18 publications

Autotaxin Downregulates LPS‐Induced Microglia Activation and Pro‐Inflammatory Cytokines Production

Autotaxin Downregulates LPS‐Induced Microglia Activation and Pro‐Inflammatory Cytokines Production

Lysophosphatidic acid (LPA) and its receptors: Role in airway inflammation and remodeling

Inhibition of lysophosphatidic acid receptors 1 and 3 attenuates atherosclerosis development in LDL-receptor deficient mice

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