Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells

2003 ◽  
Vol 284 (2) ◽  
pp. L279-L289 ◽  
Author(s):  
Susan J. Smith ◽  
Steven Brookes-Fazakerley ◽  
Louise E. Donnelly ◽  
Peter J. Barnes ◽  
Mary S. Barnette ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
T Cell ◽  
T Lymphocytes ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cardiac Myocytes ◽  
Cell Lines ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Lung Fibroblasts

We have determined the expression of phosphodiesterase (PDE) 7A1 and PDE7A2 in human cells that have been implicated in the pathogenesis of chronic obstructive pulmonary disease and asthma. Messenger RNA transcripts were detected by RT-PCR in T lymphocytes, monocytes, neutrophils, airway and vascular smooth muscle cells, lung fibroblasts, epithelial cells, and cardiac myocytes. Human epithelial, T cell, eosinophil, and lung fibroblast cell lines were also positive for PDE7A1 and PDE7A2 mRNA transcripts. By Western immunoblot analyses the amount of PDE7A1 was greatest in T cell lines, peripheral blood T lymphocytes, epithelial cell lines, airway and vascular smooth muscle cells, lung fibroblasts, and eosinophils but was not detected in neutrophils. In contrast, PDE7A2 protein, which was identified in human cardiac myocytes, was not found in any of the other cell types investigated. Immunoconfocal analyses showed that PDE7A was expressed in neutrophils and alveolar macrophages. As the expression of PDE7A mirrors the distribution of PDE4 we speculate that this enzyme could be a target for novel anti-inflammatory drugs.

Regulation of Matrix Metalloproteinase Expression in Human Vascular Smooth Muscle Cells by T Lymphocytes

1997 ◽  
Vol 81 (3) ◽  
pp. 448-454 ◽  
Author(s):  
Uwe Schönbeck ◽  
François Mach ◽  
Galina K. Sukhova ◽  
Curran Murphy ◽  
Jean-Yves Bonnefoy ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
T Lymphocytes ◽  
Matrix Metalloproteinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells

scholarly journals Orai1 and Ca2+-independent phospholipase A2 are required for store-operated Icat-SOC current, Ca2+ entry, and proliferation of primary vascular smooth muscle cells

2012 ◽  
Vol 302 (5) ◽  
pp. C748-C756 ◽  
Author(s):  
Bo Yang ◽  
Tomasz Gwozdz ◽  
Joanna Dutko-Gwozdz ◽  
Victoria M. Bolotina
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Phospholipase A2 ◽  
Cell Lines ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Multiple Functions

Store-operated Ca2+ entry (SOCE) is important for multiple functions of vascular smooth muscle cells (SMC), which, depending of their phenotype, can resemble excitable and nonexcitable cells. Similar to nonexcitable cells, Orai1 was found to mediate Ca2+-selective (CRAC-like) current and SOCE in dedifferentiated cultured SMC and smooth muscle-derived cell lines. However, the role of Orai1 in cation-selective store-operated channels (cat-SOC), which are responsible for SOCE in primary SMC, remains unclear. Here we focus on primary SMC, and assess the role of Orai1 and Ca2+-independent phospholipase A2 (iPLA2β, or PLA2G6) in activation of cat-SOC current ( Icat-SOC), SOCE, and SMC proliferation. Using molecular, electrophysiological, imaging, and functional approaches, we demonstrate that molecular knockdown of either Orai1 or iPLA2β leads to similar inhibition of the whole cell cat-SOC current and SOCE in primary aortic SMC and results in significant reduction in DNA synthesis and impairment of SMC proliferation. This is the first demonstration that Orai1 and iPLA2β are equally important for cat-SOC, SOCE, and proliferation of primary aortic SMC.

scholarly journals Regulation of the Versican Promoter by the β-Catenin-T-cell Factor Complex in Vascular Smooth Muscle Cells

2005 ◽  
Vol 280 (13) ◽  
pp. 13019-13028 ◽  
Author(s):  
Maziar Rahmani ◽  
Jason T. Read ◽  
Jon M. Carthy ◽  
Paul C. McDonald ◽  
Brian W. Wong ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
T Cell ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
T Cell Factor

Synthesis and Expression of Tissue Factor Pathway Inhibitor by Serum-stimulated Fibroblasts, Vascular Smooth Muscle Cells and Cardiac Myocytes

1999 ◽  
Vol 82 (12) ◽  
pp. 1663-1672 ◽  
Author(s):  
S. Steer ◽  
M. N. Kuppuswamy ◽  
W. Kisiel ◽  
S. P. Bajaj ◽  
M. S. Bajaj
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Tissue Factor ◽  
Cardiac Myocytes ◽  
Vascular Smooth Muscle Cells ◽  
Tissue Factor Pathway Inhibitor ◽  
Muscle Cells ◽  
Serum Stimulation ◽  
Tissue Factor Pathway

SummaryTissue factor pathway inhibitor (TFPI) plays an important role in regulating tissue factor (TF)-initiated blood coagulation. Since serum stimulation of fibroblasts, vascular smooth muscle cells and cardiac myocytes in culture increases the expression of TF mRNA and antigen (Ag) in these cells, we hypothesized that serum may also induce increased synthesis of TFPI in these cells to regulate the TF-induced extravascular clotting at an injury site. To test this concept, we used primary isolates of the following human cell types – fetal and adult lung fibroblasts, pulmonary and aortic smooth muscle cells, and cardiac myocytes. Serum-stimulation of these cells resulted in an increased expression of TF mRNA and Ag (8 to10-fold). Upon serum stimulation, expression of TFPI mRNA and Ag was also increased in these cells. However, the increase in TFPI-Ag (6 to 8-fold) was significantly greater than the TFPI mRNA (2 to 3-fold). Notably, increased expression of TFPI persisted after the TF expression had declined. Further, increased synthesis of TFPI initially led to the saturation of heparin-releasable binding sites. TFPI-Ag was detected by Western blotting, 35S-metabolic labeling and activity assays on the conditioned media, heparin-released material from cells, and in cell lysates. TFPI-Ag was also detected by immunofluorescence staining of cells. Actinomycin D partially whereas cycloheximide completely prevented the serum-induced increased expression of TFPI synthesis by these cells, suggesting control primarily at the translational but some at the transcriptional level as well. The Mr of undegraded TFPI in all cases was ~45 kDa and was of full length. TFPI synthesized locally by fibroblasts, vascular smooth muscle cells and cardiac myocytes could play a significant role in regulating TF-initiated extravascular clotting especially since plasma TFPI that may be available at the injury site lacks a portion of the carboxyl segment and is a less efficient inhibitor.

scholarly journals TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque

2006 ◽  
Vol 203 (1) ◽  
pp. 239-250 ◽  
Author(s):  
Kayoko Sato ◽  
Alexander Niessner ◽  
Stephen L. Kopecky ◽  
Robert L. Frye ◽  
Jörg J. Goronzy ◽  
...  
Keyword(s):  
T Cells ◽  
Smooth Muscle ◽  
T Cell ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Atherosclerotic Plaque ◽  
Cd4 T Cells ◽  
Muscle Cells ◽  
Immunodeficient Mice

Acute coronary syndromes (ACS) are precipitated by a rupture of the atherosclerotic plaque, often at the site of T cell and macrophage infiltration. Here, we show that plaque-infiltrating CD4 T cells effectively kill vascular smooth muscle cells (VSMC). VSMCs sensitive to T cell–mediated killing express the death receptor DR5 (TNF-related apoptosis-inducing ligand [TRAIL] receptor 2), and anti-TRAIL and anti-DR5 antibodies block T cell–mediated apoptosis. CD4 T cells that express TRAIL upon stimulation are expanded in patients with ACS and more effectively induce VSMC apoptosis. Adoptive transfer of plaque-derived CD4 T cells into immunodeficient mice that are engrafted with human atherosclerotic plaque results in apoptosis of VSMCs, which was prevented by coadministration of anti-TRAIL antibody. These data identify that the death pathway is triggered by TRAIL-producing CD4 T cells as a direct mechanism of VSMC apoptosis, a process which may lead to plaque destabilization.

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