Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of shear stress on the expression of tissue-type plasminogen activator (t-PA) in intact human conduit vessels. Human umbilical veins were exposed to high or low shear stress (25 vs < 4 dyn/cm2) at identical intraluminal pressure (20 mmHg) for 1.5, 3, and 6 h in a new computerized biomechanical perfusion system. High shear perfusion induced a marked, time-dependent increase in t-PA immunostaining in both the endothelium and the media. t-PA relative to GAPDH gene expression increased by 54 +/- 14% in high- compared to low-sheared vessels (p = 0.002). By contrast, t-PA release into the perfusion medium was similar in vessels perfused under high or low shear stress conditions. The results show that shear stress independently of pressure is a potent fluid mechanical stimulus for up-regulation of the intracellular storage pool of t-PA in the vascular wall of fresh human conduit vessels. The shear effect is associated with an increased t-PA gene expression.
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PMID:Fluid shear stress increases the intra-cellular storage pool of tissue-type plasminogen activator in intact human conduit vessels. 1095 3

Phospholipase A(2) (PLA(2)) is a growing family of enzymes that may play a major role in inflammation. We investigated the effect of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on the gene expression of 19 different PLA(2) types (IB, IIA, IID, IIE, IIF, III, IVA, IVB, IVC, V, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII, and XIII) in human bronchoepithelial (BEAS-2B) and nasal epithelial (RPMI 2650) cells. The cells were stimulated with TNF-alpha or IFN-gamma for different lengths of time (1, 4, 18, and 48 h), and the mRNA levels of the different PLA(2) types were determined by reverse transcriptase-PCR (RT-PCR) and normalized to those of the housekeeping gene, GAPDH. In both cell lines, TNF-alpha increased the expression of PLA(2) IVA and IVC, and IFN-gamma increased the expression of PLA(2) IIA and IID. No influence on the gene expression of PLA(2)-activating protein (PLAP) was noted on cytokine stimulation. These findings indicate that TNF-alpha and IFN-gamma induce gene expression of two novel cytosolic and secretory PLA(2) types (IVC and IID, respectively) in human airway epithelial cells. The possibility that these PLA(2) types are involved in cytokine-mediated inflammation in the respiratory tract is inferred.
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PMID:Increased gene expression of novel cytosolic and secretory phospholipase A(2) types in human airway epithelial cells induced by tumor necrosis factor-alpha and IFN-gamma. 1239 16

Phospholipase A(2) (PLA(2)) is a superfamily of enzymes that may play a major role in airways inflammation. We investigated the effect of interferon-gamma (IFN-gamma) on the gene expression of 19 different PLA(2) types in human monocyte-derived macrophages and nasal epithelial cells (RPMI 2650). The cells were stimulated with IFN-gamma for different lengths of time (up to 48 h), and the mRNA levels of the different PLA(2) types were determined by reverse transcriptase-PCR (RT-PCR) and normalized to those of the house-keeping gene, GAPDH. It appeared that IFN-gamma clearly increased the expression of secretory PLA(2) IID (but not IIA) in macrophages, while both PLA(2) IID and IIA were upregulated in RPMI 2650 cells. Moreover, after 18 h, the mRNA levels of cytosolic PLA(2) IVA were 2-3 times higher in IFN-gamma-stimulated macrophages than controls, while there was no such effect of IFN-gamma in RPMI 2650 cells. Lipopolysaccharide (LPS) augmented the increased gene expression of PLA(2) IVA but decreased both the basal and the IFN-gamma-induced PLA(2) IID mRNA expression in macrophages (but not in RPMI 2650 cells). The NF-kappaB inhibitor Pyrrolidine dithiocarbamate (PDTC) and the phoshatidylinositol 3-kinase (PI3K) inhibitor wortmannin were employed to get an insight into the mechanism behind these observations. Incubation of macrophages with PDTC had no effect on the LPS impairment of PLA(2) IID gene expression, but inhibited the LPS mediated activation of PLA(2) IVA. No significant effect was noted of PDTC on IFN-gamma stimulation, while PI3K had no effect at all on any of the stimuli used. Furthermore, LPS (but not IFN-gamma) increased the mRNA levels of the nuclear factor (NF)-kappaB inhibitors alpha and xi in macrophages, but not in RPMI 2650 cells. These findings indicate that (a) the gene expression of secretory types PLA(2) IID and IIA in response to IFN-gamma is much dependent on cell type, and (b) the regulation of PLA(2) type IID in human macrophages is clearly different from that of PLA(2) type IVA. (c) PLA(2) IVA is probably under control of both NF-kappaB and IFN-gamma-responsive elements (GRE) or IFN-gamma-activating sites (GAS). The possibility that PLA(2) IID is involved in cytokine-mediated inflammation in the nasal mucosa is inferred, as is the potential role of PLA(2) IID in the host defense against LPS-containing bacteria.
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PMID:Interferon gamma-induced gene expression of the novel secretory phospholipase A2 type IID in human monocyte-derived macrophages is inhibited by lipopolysaccharide. 1689 54

Dirofilaria immitis is the causative agent of canine and feline heartworm disease. The parasite can survive for long periods of time (7 years or more) in the circulatory system of immunocompetent reservoirs, producing usually a chronic inflammatory vascular disease. In addition, the simultaneous death of groups of adult worms can trigger an acute disease characterized by the exacerbation of inflammatory reactions and the emergence of serious thromboembolic events. In the context of the D. immitis/host relationships, the aim of this study was to investigate the interaction between the excretory/secretory antigens from D. immitis adult worms (DiES) and the fibrinolytic system of the host. Using an enzyme-linked immunosorbent assay we showed that DiES extract is able to bind plasminogen and generate plasmin, although this fact requires the presence of the tissue plasminogen activator (t-PA). Moreover, we established that DiES extract enhances t-PA expression in cultured vascular endothelial cells. Additionally, 10 plasminogen-binding proteins from DiES extract were identified by mass spectrometry (HSP60, actin-1/3, actin, actin 4, transglutaminase, GAPDH, Ov87, LOAG_14743, galectin and P22U). The data suggest that DiES antigens interact with the environment of the parasite regulating the activation of the fibrinolytic system of the host with involvement of the vascular endothelium in the process.
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PMID:Excretory/secretory antigens from Dirofilaria immitis adult worms interact with the host fibrinolytic system involving the vascular endothelium. 2205 Sep 27

Cardiopulmonary dirofilariosis (Dirofilaria immitis) is characterized by apparent contradictory events, like the long-term survival of adult worms in the circulatory system of the infected hosts and the development of life-threatening events like thromboembolisms and others. Thus parasite mechanisms, like the activation of fibrinolytic system, are key to the survival of both the worms and the host. The aim of this study was to investigate the interaction between D. immitis adult worms surface-associated antigens (DiSAA) and the fibrinolytic system of the host. We demonstrate that DiSAA extract is able to bind plasminogen and generate plasmin, with the latter occurring in a tissue plasminogen activator (t-PA) dependent manner. Additionally, 11 plasminogen-binding proteins from DiSAA extract were identified by proteomics and mass spectrometry (MS) (actin-5C, actin-1, enolase, fructose-bisphosphate aldolase, GAPDH, MSP domain protein, MSP 2, beta-galactosidase-binding-lectin, galectin, immunoglobulin I-set domain-containing protein and cyclophilin Ovcyp-2). Because in a previous work we have shown the positive interaction between the excretory/secretory antigens of D. immitis (DiES) and the host fibrinolytic system and many of the molecules identified here are shared by both antigens, we hypothesize that DiSAA cooperate in host fibrinolytic system activation promoting the fibrin clot lysis.
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PMID:Surface associated antigens of Dirofilaria immitis adult worms activate the host fibrinolytic system. 2343 49