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)

Plasminogen activators and their inhibitors are thought to play an important role in the regulation of a variety of pathologic processes including inflammation and wound healing. IL-1 is one inflammatory mediator which has been shown to increase release of plasminogen activator (PA) Ag and activity by mesenchymal cells such as chondrocytes and synoviocytes. We have found that rIL-1 beta induces a rapid and significant accumulation of both tissue-and urinary-type plasminogen activator (t-PA and u-PA) mRNA and type 1 and 2 plasminogen activator inhibitor (PAI-1 and PAI-2) mRNA in MRC-5 fetal lung fibroblasts. An SV40 transformed fibroblast cell line, XP12RO, showed an identical response of PAI-1 and t-PA message levels but revealed no change in PAI-2 or u-PA mRNA levels with rIL-1 beta stimulation. Treatment with the transcriptional inhibitor actinomycin D blocked accumulation of t-PA, u-PA, PAI-1, and PAI-2 mRNA, suggesting that RNA synthesis is required for accumulation of all four transcripts. Cycloheximide (CHX) treatment altered the rate of PAI-1 and t-PA mRNA accumulation, but both were able to increase in the absence of protein synthesis. CHX blocked the rIL-1 beta-induced increase in PAI-2 mRNA levels normally observed at 8 h, indicating that protein synthesis is required for this response to IL-1. The increase in u-PA message level was augmented in a synergistic fashion by CHX. These data for PAI-2 and u-PA provide evidence for short-lived proteins which act either to modulate transcription of these genes or regulate mRNA stability. Thus plasminogen activators and their inhibitors are regulated in a positive and complex fashion in the fibroblast by IL-1, suggesting an important role for these molecules and this cell type in the response to inflammation.
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PMID:Modulation of mRNA levels for urinary- and tissue-type plasminogen activator and plasminogen activator inhibitors 1 and 2 in human fibroblasts by interleukin 1. 250 87

The human diploid fibroblast cell line, MRC-5, derived from embryo lung tissue produced only small quantities of plasminogen activator (PA) when harvested using a standard nutrient medium (Eagle's Minimal Essential Medium, MEM). Use of a schedule designed to induce high concentrations of fibroblast interferon in these cells also resulted in production of considerably enhanced levels of PA. The kinetics of PA production differed from those of interferon production; specifically, PA was produced for at least 6 days following induction despite the toxicity of the inducers whereas interferon synthesis continued for only 1 day. Further investigation of the induction conditions for PA revealed that double-stranded RNA which was absolutely required for interferon production was not required for induction of PA. Indeed, the stimulus for enhancement of PA production appeared to be solely an elevated concentration of calcium ions in the extracellular medium. The possible physiological relevance of this induction of PA by elevated concentrations of calcium ions is discussed.
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PMID:Induction of plasminogen activator in a human diploid fibroblast cell line (MRC-5) by conditions which cause induction of interferon: the role of calcium ions. 653 47

The expression of transformation parameters (inhibition of cell division during cell crowding, anchorage dependence, loss of fibrin clot retractile activity and secretion of plasminogen activator) was studied in a heterospecific cellular hybrid, made between established L(TK-) cells and the normal human MRC-5 cells. The hybrid nature of the cross was confirmed by the ability to incorporate [3H]-thymidine, by growth in selective HAT medium, by the identification of human chromosomes and by the expression on the surface of 100% of hybrid cells of a human glycoprotein, which is recognized by the 4F2 monoclonal antibody. The hybrid cultures showed cell cycle inhibition which became less stringent with increasing population doublings and the loss of human chromosomes. Fibrin clot retraction and anchorage dependence were absent in spite of the presence of many human chromosomes. The two properties were present or lost simultaneously in the normal parent cells and in the transformed parent or hybrid cells respectively. The human type of plasminogen activator was secreted even with very little human genetic material left, and a complete dissociation between fibrin clot retraction and production of plasminogen activator was observed. The data strengthen the hypothesis that transformation is a multistep process that involves complex genetic control and where cells progressively express different phenotypes and escape growth control.
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PMID:Comparison of fibrin clot retraction with other transformation parameters after hydridization of normal and established cell lines. 668 7

Phospholipases A(2) are components of Bothrops venoms responsible for disruption of cell membrane integrity via hydrolysis of its phospholipids. This study used a large nonimmune human scFv library named Griffin.1 (MRC, Cambridge, UK) for selection of recombinant antibodies against antigens present in Bothrops jararacussu venom and identification of specific antibodies able to inhibit phospholipase activity. Four clones were identified as capable of inhibiting this activity in vitro. These clones were able to reduce in vivo the myotoxic activity of BthTX-I and BthTX-II PLA(2), but had no effect on the in vitro anticoagulant activity of BthTX-II. This work shows the potential of using recombinant scFv libraries in the search for antibodies that neutralize relevant venom components.
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PMID:Expression of recombinant human antibody fragments capable of inhibiting the phospholipase and myotoxic activities of Bothrops jararacussu venom. 1682 72

Proto-oncogene survivin has recently been identified as a prognostic marker distinguishing patients with destructive rheumatoid arthritis (RA). In the present material of 132 RA patients and 82 controls, the levels of survivin correlated to urokinase (uPA) (r= 0.46), a plasminogen activator over-expressed in inflamed joints and known to exhibit potent arthritogenic properties. Here we evaluate the functional relationship between these proteins using primary synovial fibroblasts and leucocytes of RA patients, human monocytic (THP-1) and fibroblast (MRC-5) cell lines. Using inhibitors of intracellular signalling, we show that uPA and survivin share common transduction pathways in synovial fibroblasts being dependent on the activity of tyrosine kinases, phosphatidylinositide 3 kinase and mitogen effector kinase. Moreover, uPA production is significantly reduced in fibroblasts if survivin synthesis has been silenced by siRNA. Importantly, silencing of survivin in fibroblasts prevented their invasive growth in knee joints of severe combined immune deficient mice. Interaction of uPA with receptor up-regulates survivin expression in leucocytes. In turn, survivin is required for the up-regulation of uPA receptor on the cell surface. These findings indicate that survivin is an essential mediator of arthritogenic properties of uPA regulating its synthesis in synovial fibroblasts and uPAR expression in leucocytes. Close correlation between survivin and uPA levels in patients with RA supports the importance of this connection for the pathogenesis of arthritis.
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PMID:Survivin is an essential mediator of arthritis interacting with urokinase signalling. 1929 27