Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphodiesterase inhibitors possess anti-inflammatory and immunomodulatory properties and seem to have a great potential in the treatment of inflammatory skin diseases; however, an overall study on the effects of specific phosphodiesterase inhibitors, such as rolipram on the processes involved in the extravasation of lymphoid cells has not been performed. In this work we have assessed the effect of rolipram on the adhesion, polarization, and migration of normal human T lymphocytes. We found that low concentrations of rolipram were able to inhibit significantly the adhesion of T cells to the beta1 and beta2 integrin ligands vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. Rolipram also interfered with the activation of integrins, and significantly inhibited the homotypic aggregation of T lymphocytes induced by anti-beta1 and anti-alpha4 integrin chain monoclonal antibodies. In addition, rolipram had a downregulatory effect on the activation of T cells, and significantly diminished the expression of the activation antigens CD69, CD25, and CD98 induced by phytohemagglutinin. Finally, this drug inhibited the polarization and transendothelial migration of T lymphocytes induced by the chemokine CXCL12 (SDF-1) and the chemotactic cytokine interleukin-15. The results indicate that rolipram, at low concentrations, exerts an important anti-inflammatory and immunomodulatory effect, and suggest that this selective phosphodiesterase inhibitor may be an effective tool for the therapy of immune-mediated diseases.
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PMID:Rolipram inhibits polarization and migration of human T lymphocytes. 1283 67

Autotaxin (ATX/NPP2) is a tumor cell motility-stimulating factor that displays both a nucleotide pyrophosphatase/phosphodiesterase activity and a recently described lysophospholipase D (lysoPLD) activity. The precise function of ATX in tumor cells and the role of ATX in thyroid carcinoma remains unclear. We have quantified ATX mRNA expression in thyroid carcinoma cell lines and in tissues of patients with thyroid carcinomas. ATX gene activity was significantly higher in undifferentiated anaplastic thyroid carcinoma cell lines (UTC) and tumor tissues as compared to follicular thyroid carcinoma (FTC) cell lines, FTC tissues or goiter tissues that were used as a control. In the thyroid carcinoma cell line 1736, EGF and bFGF stimulated ATX mRNA expression, whereas the cytokines IL-4, IL-1beta and TGF-beta reduced ATX transcriptional levels. FTC-133 cells, stably transfected with an expression vector for ATX, showed a higher lysoPLD activity, a higher proliferation rate and an increased migratory behavior. In addition, ATX also displayed a paracrine stimulatory effect on the motility of different thyroid carcinoma cell lines. Overexpression of ATX in the stably transfected FTC-133 resulted in down-regulation of CD54/ intercellular adhesion molecule-1 (ICAM-1) gene expression and augmented gene activity of the pro-angiogenic chemokine IL-8. We conclude that ATX may be regarded as a new tissue marker for undifferentiated human thyroid carcinoma cells. ATX increases the proliferation and migration of thyroid carcinoma cell lines and may also affect the angiogenic potential of thyroid carcinoma cells. Further studies are needed to provide insight into the role of ATX in the normal and neoplastic thyroid gland.
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PMID:Expression, regulation and function of autotaxin in thyroid carcinomas. 1502 16

We investigated the possible therapeutic effect of cilostazol, a specific inhibitor of phosphodiesterase-3, for experimental autoimmune encephalomyelitis (EAE). Mice affected with EAE induced by inoculation with MOG(35-55) were fed with cilostazol or vehicle control. The clinical EAE scores of the cilostazol-fed mice were lower than those of the controls. Serum level of soluble intercellular adhesion molecule-1 was significantly lower in the cilostazol-fed mice than in the controls. In the recall responses with MOG(35-55), proliferation and IFN-gamma production by lymphocytes from cilostazol-fed mice were significantly reduced. Cilostazol may exhibit repressive effects on EAE by reducing the antigen-specific T-cell response and decreasing the expression of the adhesion molecules. Cilostazol is a hopeful choice for the treatment of multiple sclerosis.
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PMID:Selective phosphodiesterase-3 inhibitor cilostazol ameliorates experimental autoimmune encephalomyelitis. 1940 18


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