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)

To examine the participation of the theca-interstitial (TI) compartment in cytokine modulation of ovarian function, the effects of interleukin-1beta (IL-1) on plasminogen activator (PA) activity and on prostaglandin E (PGE) and nitric oxide (NO) production were examined in cultures of pregnant mare serum gonadotrophin (PMSG)-primed rat TI cells. Exposure to IL-1 (10 ng/ml) resulted in a 25% reduction (P < 0.001) in PA activity, concurrent with a 4.6-fold increase in the ability of the corresponding conditioned media to inhibit exogenous urokinase activity. IL-1 also produced a 4.7-fold increase in PGE content and a 2.8-fold increase in NO generation. These effects of IL-1 were abolished by the IL-1 receptor antagonist, suggesting specific IL-1 receptor-mediated effects. Transforming growth factor (TGF)-beta1 (10 ng/ml) significantly attenuated the IL-1-stimulated PGE production and NO generation but did not affect the ability of IL-1 to suppress PA activity and stimulate urokinase inhibitor production. The NO synthase inhibitor N-nitro-L-arginine attenuated the IL-1-induced NO generation but had no effect on PA activity or PGE production. Thus, NO is not an obligatory mediator of IL-1 effects on plasminogen activation and PGE generation in rat ovary. The present observations attest to a pleiotropic response of PMSG-primed TI cells to IL-1, and suggest a paracrine/autocrine function for the TI compartment in ovulation and corpus luteum formation.
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PMID:In-vitro modulation of plasminogen activator activity, prostaglandin E and nitric oxide production by interleukin-1 in pregnant mare serum gonadotrophin-primed theca-interstitial cells. 915 41

We examined whether shear stress can inhibit vascular smooth muscle cell (VSMC) proliferation in vitro directly. Human VSMCs were exposed to fluid flow for 24 hours using a cone-plate apparatus, and their proliferation was inhibited significantly by shear stresses of 1.4 and 2.8 Pa (14 and 28 dyne/cm2), according to the magnitude. Next, we investigated whether transforming growth factor-beta 1 (TGF beta 1), which is known to be an important cytokine that suppresses VSMC proliferation, is the predominant mediator of shear-induced inhibition of VSMC growth. After exposure of VSMCs to shear stress (2.8 Pa) for 24 hours, gene expression of TGF beta 1 and, interestingly, tissue-type plasminogen activator, which converts plasminogen to plasmin, an activator of TGF beta 1, increased twofold and fivefold, respectively. The levels of both latent and active forms of TGF beta 1 in conditioned media of VSMCs exposed to fluid flow increased significantly. An anti-TGF beta 1 antibody reversed shear-induced inhibition of VSMC growth significantly. We concluded that shear stress inhibited VSMC proliferation in vitro and this inhibition was mediated predominantly by TGF beta 1 in an autocrine manner. These data suggest that shear stress plays an important role as an inhibitor of atherogenesis in endothelium-desquamated lesions.
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PMID:Shear stress as an inhibitor of vascular smooth muscle cell proliferation. Role of transforming growth factor-beta 1 and tissue-type plasminogen activator. 930 28

A decreased fibrinolytic activity of serosal surfaces appears to be a major factor in the development of peritoneal fibrous adhesions. Serosal fibrinolysis is regulated by mesothelial release of tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI-2). We investigated the influence of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta1) and interleukin 1beta (IL-1beta) on pro- and antifibrinolytic properties of mesothelial cells (HOMC) using a cell/fibrin clot assay. TGF-beta1, TNF-alpha and IL-1beta induced a dose dependent 2.9, 2.3 and 1.9-fold increase of PAI-1 antigen, respectively, whereas t-PA concentrations decreased to one third of the control values. This modified PAI-1/t-PA secretion pattern leads to a significant delay of fibrinolysis. Analysis of m-RNA levels revealed increased PAI-1 m-RNA concentrations after 12 h and decreased m-RNA concentrations for t-PA after 6 h. Serosal hypofibrinolysis during peritonitis may be explained at least in part by cytokine effects which thus may favor adhesion formation.
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PMID:Modulation of pro- and antifibrinolytic properties of human peritoneal mesothelial cells by transforming growth factor beta1 (TGF-beta1), tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta). 949 92

Previous studies suggested indirectly that residual bodies (RB) may play a role in the regulation of the proteolytic system within the testis and in the coordination of the spermatogenetic process. In the present study, we examined the effects of RB recovered from adult rat testes by centrifugal elutriation on Sertoli cell plasminogen activator (PA) levels, by zymography and ELISA procedures. Addition of RB to Sertoli cell cultures prepared from 20-day-old rat testes resulted in a dramatic stimulation of PA. Effects were dose- and time-dependent. Phagocytosis of RB by Sertoli cells leads to a rapid stimulation of Sertoli cell interleukin-1alpha (IL-1alpha), a cytokine potentially involved in the regulation of spermatogenesis; the effects of IL-1alpha were investigated. We found that IL-1alpha augmented PA levels and that immunodepletion of Sertoli cell-RB cocultures with anti-IL-1alpha antibodies abrogated the stimulatory effects of RB on PA. Together, the present findings indicate that RB enhance Sertoli cell PA and that IL-1alpha may be involved in that control.
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PMID:Residual bodies stimulate rat Sertoli cell plasminogen activator activity. 973 31

Vascular endothelial growth factor-C (VEGF-C) is a recently characterized member of the VEGF family of angiogenic polypeptides. We demonstrate here that VEGF-C is angiogenic in vitro when added to bovine aortic or lymphatic endothelial (BAE and BLE) cells but has little or no effect on bovine microvascular endothelial (BME) cells. As reported previously for VEGF, VEGF-C and basic fibroblast growth factor (bFGF) induced a synergistic in vitro angiogenic response in all three cells lines. Unexpectedly, VEGF and VEGF-C also synergized in the in vitro angiogenic response when assessed on BAE cells. Characterization of VEGF receptor (VEGFR) expression revealed that BME, BAE, and BLE cell lines express VEGFR-1 and -2, whereas of the three cell lines assessed, only BAE cells express VEGFR-3. We also demonstrate that VEGF-C increases plasminogen activator (PA) activity in the three bovine endothelial cell lines and that this is accompanied by a concomitant increase in PA inhibitor-1. Addition of alpha2-antiplasmin to BME cells co-treated with bFGF and VEGF-C partially inhibited collagen gel invasion. These results demonstrate, first, that by acting in concert with bFGF or VEGF, VEGF-C has a potent synergistic effect on the induction of angiogenesis in vitro and, second, that like VEGF and bFGF, VEGF-C is capable of altering endothelial cell extracellular proteolytic activity. These observations also highlight the notion of context, i.e., that the activity of an angiogenesis-regulating cytokine depends on the presence and concentration of other cytokines in the pericellular environment of the responding endothelial cell.
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PMID:Vascular endothelial growth factor (VEGF)-C synergizes with basic fibroblast growth factor and VEGF in the induction of angiogenesis in vitro and alters endothelial cell extracellular proteolytic activity. 980 52

The overall fibrinolytic activity is depressed in patients with chronic renal failure where a prothrombotic state is described, thereby enhancing the risk of vascular occlusive events. The mechanism responsible for fibrinolysis derangement has not yet been elucidated. To evaluate the effect of the uremic environment on the fibrinolytic activity of endothelial cells, we studied plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) production by human umbilical vein endothelial cells (HUVEC) in culture, exposed either to uremic or normal sera, before and after cytokine stimulation. Twenty uremics were studied: 11 were on conservative dietary treatment and nine were on maintenance hemodialysis. Eight healthy subjects served as controls. Before cytokine stimulation, no difference in the HUVEC supernatant concentration of t-PA and PAI-1 was found among the groups studied. After stimulation with interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, the HUVEC supernatant levels of PAI-1 in the uremics were higher than in the controls, whereas the supernatant levels of t-PA did not differ. Our data provide evidence that uremic serum, in concert with IL-1 or TNF-alpha, can enhance PAI-1 secretion by endothelial cells, thereby depressing the fibrinolytic system. This impaired endothelial fibrinolytic response to hypercoagulation could favor vascular events, which are the major cause of morbidity and mortality in patients with chronic uremia.
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PMID:Uremic medium increases cytokine-induced PAI-1 secretion by cultured endothelial cells. 980 72

Clinical trials with monoclonal antibodies directed against TNF alpha (anti-TNF mAbs) and soluble TNF receptor fusion proteins (sTNFR-IgGs) have demonstrated that systemic and synovial trapping of TNF alpha results in long lasting anti-inflammatory and anti-nociceptive effects in patients with rheumatoid arthritis. Clinical indices of inflammatory synovitis and laboratory parameters (CRP and ESR) respond to single and repeated administrations of anit-TNF alpha therapies in a dose-dependent fashion. Studies on the immuno-pharmacological profile in patients suggest evidence that TNF alpha trapping down-regulates the effector mechanisms involved in the immuno-inflammatory response in rheumatoid arthritis. Inhibition of PLA 2- and COX-2-derived pathways of mediators of inflammation (prostanoids and leukotrienes) decreases signs and symptoms of inflammatory synovitis such as joint swelling, tenderness and pain. Down-regulating of the cytokine-inducible adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in endothelial cells and synoviocytes results in a marked inhibition of transendothelial migration of inflammatory and immune cells. A decrease of cytokine-regulated metalloproteinase expression results in normalization of circulating MMP-1 and MMP-3 levels. The effect of TNF alpha neutralization on mechanisms of rheumatoid joint destruction has the long-term potential for preventing or decreasing the rate of erosive changes of cartilage and bone.
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PMID:[Immunopharmacologic profile and therapeutic prospects of anti-TNF-alpha therapy]. 986 33

To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 microg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked antiinflammatory cytokine response (IL-10, soluble tumor necrosis factor [TNF] receptors, IL-1 receptor antagonist) and secretion of alpha-chemokines (IL-8, IFN-gamma-inducible protein 10) and beta-chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta). In addition, IL-12 elicited neutrophilic leukocytosis, neutrophil degranulation (elastase-alpha1-antitrypsin complexes), coagulation activation (F1 + 2 prothrombin fragment, thrombin-antithrombin III complexes), and fibrinolytic activation (tissue-type plasminogen activator, plasmin-alpha2-antiplasmin complexes). IL-12-induced activation of multiple host mediator systems was found only after 8-24 h, remained detectable until the end of the 48-h observation period, and occurred in the absence of detectable TNF and IL-1beta. These data may contribute to understanding the role of IL-12 in the pathogenesis of sepsis syndrome and the toxicity found after repeated injections of IL-12.
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PMID:Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees. 995 71

The temporal and spatial expression in brain of the mRNAs for the pleiotropic cytokine hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-met were compared to those of a known HGF/SF activator, tissue-type plasminogen activator (tPA). In addition to the previously described expression in the developing and adult olfactory system [D.P. Thewke, N.W. Seeds, Expression of hepatocyte growth factor/scatter factor, its receptor, c-met, and tissue-type plasminogen activator during development of the murine olfactory system, J. Neurosci. 16 (1996) 6933-6944] two other regions of the mouse brain were found where the expression of tPA mRNA appeared to co-localized with HGF/SF and/or c-met mRNA. In the developing hippocampus, tPA mRNA was expressed coincident with HGF/SF and c-met mRNAs in the CA1 field. tPA mRNA was expressed in all areas of the adult hippocampus, while HGF/SF expression was restricted to the CA2 and CA3 fields, and c-met mRNA was seen primarily in the CA1 field. In the developing cerebral cortex, the expression of tPA mRNA was observed in the subplate and inner cortical plate between two layers of c-met expression, whereas HGF/SF mRNA was localized to the proliferative zone lining the lateral ventricle. Layer specific expression of both HGF/SF and c-met mRNA were observed in the adult cortex, where HGF/SF was expressed in layers IV and V and c-met in layers II-III, IV and V. The expression of tPA mRNA in the adult cortex was low and not layer specific, although homogenates of adult cortex did have detectable levels of tPA activity when subjected to zymography. Immunohistochemical analysis using HGF/SF and c-met antibodies on adult brain sections showed a distribution similar to the in situ hybridization results. C-met antibodies appeared to stain large neurons in the cortex and hippocampus. These results are consistent with the hypothesis that HGF/SF plays a role in the development and maintenance of both the cerebral cortex and hippocampus, and that tPA may act as a regulator of HGF/SF activity in these structures.
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PMID:The expression of mRNAs for hepatocyte growth factor/scatter factor, its receptor c-met, and one of its activators tissue-type plasminogen activator show a systematic relationship in the developing and adult cerebral cortex and hippocampus. 1006 22

Transforming growth factor-beta1 (TGF-beta1) is a critical cytokine for cell proliferation and differentiation. It is secreted by many cells in a latent pro-form (LTGF-beta1) from which biologically active TGF-beta1 is released by an in vivo mechanism that is not known. Here we show that the mannose-6-phosphate/insulin-like growth factor II-receptor (M6P/IGFII-R), which binds LTGF-beta1, complexes with urokinase (plasminogen activator)-receptor (uPA-R) on the surface of human monocytes and directly binds plasminogen (Plg). Plasmin generated from Plg in the complex mediates release of TGF-beta1 when M6P/IGFII-R is associated with uPA-R. Thus, this interaction of M6P/IGFII-R and uPA-R suggests a potential mechanism for the generation of TGF-beta1 by cells.
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PMID:M6P/IGFII-receptor complexes urokinase receptor and plasminogen for activation of transforming growth factor-beta1. 1009 5


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