Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma

Zhao, Yutong; Tong, Jiankun; He, Donghong; Pendyala, Srikanth; Berdyshev, Evgeny; Chun, Jerold; Sperling, Anne I.; Natarajan, Viswanathan

doi:10.1186/1465-9921-10-114

Cited by 59 publications

(78 citation statements)

References 54 publications

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“…Chemical conversion of lysophospholipid such as LPC to LPA can also occur in the presence of strong acid ( 26 ). The most commonly reported sample preparation method for LPA extraction from biological fl uids involves LLE with acidification ( 3,12,14,15,18,19,(27)(28)(29). Scherer et al showed that under strong acidic conditions, LPC degrades to LPA in the presence of plasma, and the total LPA concentration in human plasma was almost 10-fold higher in plasma extracted under acidic conditions versus plasma extracted polypropylene microcentrifuge tube) was spiked with 10 µl of internal standard (IS) (C17:0-LPA) working solution (in methanol) followed by 200 ul of extraction buffer (30 mM citrate/40 mM sodium phosphate in water) and 600 µl of butanol.…”

Section: Methodsmentioning

confidence: 99%

Challenges in accurate quantitation of lysophosphatidic acids in human biofluids

Onorato

Shipkova

Minnich

et al. 2014

Journal of Lipid Research

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Section: Methodsmentioning

confidence: 99%

Challenges in accurate quantitation of lysophosphatidic acids in human biofluids

Onorato

Shipkova

Minnich

et al. 2014

Journal of Lipid Research

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“…GPCR is the largest class of transmembrane receptors in the human genome involved in regulation of proliferation, differentiation, and immune response through the wide variety of its ligands [124]. One of them is lysophosphatidic acid (LPA), a bioactive phospholipid that is a component of normal plasma and biological fluids, such as saliva and bronchoalveolar fluid [125,126]. LPA is capable of inducing diverse cellular responses by inducing activity of several transcription factors, including NF-κB and AP-1 [127].…”

Section: Carma3-mediated Nf-κb Signaling Pathwaysmentioning

confidence: 99%

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

176

201

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The NF-κB family of transcription factors plays a crucial role in cell activation, survival and proliferation. Its aberrant activity results in cancer, immunodeficiency or autoimmune disorders. Over the past two decades, tremendous progress has been made in our understanding of the signals that regulate NF-κB activation, especially how scaffold proteins link different receptors to the NF-κB-activating complex, the IκB kinase complex. The growing number of these scaffolds underscores the complexity of the signaling networks in different cell types. In this review, we discuss the role of scaffold molecules in signaling cascades induced by stimulation of antigen receptors, G-protein-coupled receptors and C-type Lectin receptors, resulting in NF-κB activation. Especially, we focus on the family of Caspase recruitment domain (CARD)-containing proteins known as CARMA and their function in activation of NF-κB, as well as the link of these scaffolds to the development of various neoplastic diseases through regulation of NF-κB.

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“…High concentrations of the lipid have been detected in the bronchoalveolar lavage fluid of preclinical animal models of allergic asthma (4). LPA plays a role in regulating the secretion of pro-and anti-inflammatory mediators by airway epithelial cells and in modulating airway epithelial barrier integrity (5).…”

mentioning

confidence: 99%

Rho Kinase-2 Activation in Human Endothelial Cells Drives Lysophosphatidic Acid-mediated Expression of Cell Adhesion Molecules via NF-κB p65

Shimada

Rajagopalan

2010

Journal of Biological Chemistry

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The trans-endothelial migration of activated leukocytes into inflamed tissue is an important mechanism in the pathogenesis of inflammatory diseases. Endothelial cells play a key role in this step by up-regulating the synthesis and secretion of chemokines and the cell surface expression of adhesion molecules (CAMs) 2 (1). The adhesion molecules ICAM-1 and VCAM-1 bind leukocytes expressing the major integrins lymphocyte function associated antigen-1 (LFA-1) and the VLA-4 (very late activation antigen-4), respectively, and are induced on endothelial cells by inflammatory stimuli (2, 3). Both are required for the attachment of circulating leukocytes to the endothelium and mediate not only transcellular migration but also the induction of intracellular signals resulting in transient junctional disruption (1) and the paracellular passage of leukocytes across the endothelial monolayer.Lysophosphatidic acid (LPA), a pleiotropic proinflammatory lipid mediator, is elevated in multiple disease states. High concentrations of the lipid have been detected in the bronchoalveolar lavage fluid of preclinical animal models of allergic asthma (4). LPA plays a role in regulating the secretion of pro-and anti-inflammatory mediators by airway epithelial cells and in modulating airway epithelial barrier integrity (5). Additionally, synovial fluid obtained from rheumatoid arthritis patients contain significant amounts of LPA and the LPA-synthesizing enzyme autotaxin driving cytokine secretion by and migration of resident synoviocytes (6, 7). The lipid mediator has also been implicated in the initiation of neuropathic pain (8). Blood platelets also store LPA and are an important source of the lipid. Serum and plasma contain nanomolar levels of LPA and de novo generation or release from platelet stores during inflammation may result in higher LPA levels at disease loci. LPA engages a family of at least five closely related G protein-coupled receptors LPA1-5 (9). It has been reported that HUVECs express LPA1 and LPA3 receptors and are responsive to LPA with induced expression of chemokines and cell adhesion molecules (CAMs) (10 -12). In vitro and in vivo studies employing Rho kinase inhibitors, isoform-specific LPA receptor inhibitors, and targeted receptor deletions link LPA acting through the LPA1 receptor, to the downstream activation of Rho kinase (8,13,14).Rho kinase, a serine/threonine kinase, was initially characterized as a mediator of the formation of RhoA-induced stress fibers and focal adhesions (15). Activation of the Rho kinase pathway leads to the phosphorylation of downstream substrates including the 20-kDa myosin light chain (MLC) (16), the myosin phosphatase subunit (MYPT-1) (17), and CPI-17A (18), which have been postulated to control a variety of fundamental cellular functions such as proliferation, survival, contraction, migration, and the transcriptional regulation of gene expression. However, abnormal activation of the pathway has been * This work was supported by Pfizer, Inc.

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Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma

Cited by 59 publications

References 54 publications

Challenges in accurate quantitation of lysophosphatidic acids in human biofluids

Challenges in accurate quantitation of lysophosphatidic acids in human biofluids

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Rho Kinase-2 Activation in Human Endothelial Cells Drives Lysophosphatidic Acid-mediated Expression of Cell Adhesion Molecules via NF-κB p65

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