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)

Previous studies have reported that the levels of pro-inflammatory cytokines, such as TNF-alpha and IFN-gamma, are elevated in the serum as well as in the cerebrospinal fluid of HAM/TSP patients. To evaluate the effect of the phosphodiesterase type IV inhibitor, rolipram on cytokine production, peripheral blood mononuclear cells (PBMCs) of HAM/TSP patients or HTLV-I infected T-cell lines (HUT102, MT2) were cultured in the presence of different doses of rolipram. The amount of cytokines in the supernatants of the cultured cells was determined by ELISA for TNF-alpha, IFN-gamma and TGF-beta. Rolipram inhibited TNF-alpha production by HUT102 and PBMCs from all the HAM/TSP patients in a dose-dependent manner. The suppression of IFN-gamma varied and was weaker in some HAM/TSP patients compared to that of TNF-alpha. The concentration of TGF-beta in the culture supernatants was not influenced by rolipram. The levels of TNF-alpha mRNA determined by competitive PCR were not changed in the cultured cells in the presence of rolipram, suggesting that rolipram inhibits TNF-alpha production at the post-transcriptional level. These findings suggest the possible benefit of rolipram as a therapeutic agent for HAM/TSP patients.
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PMID:The effect of rolipram on the production of cytokines in HTLV-I infected cell lines and peripheral blood mononuclear cells of patients with HTLV-I-associated myelopathy (HAM). 912 94

Intracellular cyclic AMP, determined in part by cyclic nucleotide phosphodiesterases (PDEs), regulates proliferation and immune functions in lymphoid cells. Total PDE, PDE3, and PDE4 activities were measured in phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC-PHA), normal natural killer (NK) cells, Jurkat and Kit225-K6 leukemic T-cells, T-cell lines transformed with human T-lymphotropic virus (HTLV)-I (a retrovirus that causes adult T-cell leukemia/lymphoma) and HTLV-II (a nonpathogenic retrovirus), normal B-cells, and B-cells transformed with Epstein-Barr virus (EBV). All cells exhibited PDE3 and PDE4 activities but in different proportions. In EBV-transformed B cells, PDE4 was much higher than PDE3. HTLV-I+ T-cells differed significantly from other T-lymphocyte-derived cells in also having a higher proportion of PDE4 activities, which apparently were not related to selective induction of any one PDE4 mRNA (judged by reverse transcription-polymerase chain reaction) or expression of the HTLV-I regulatory protein Tax. In MJ cells (an HTLV-I+ T-cell line), Jurkat cells, and PBMC-PHA cells, the tyrosine kinase inhibitor herbimycin A strongly inhibited PDE activity. Growth of MJ cells was inhibited by herbimycin A and a protein kinase C (PKC) inhibitor, and was arrested in G1 by rolipram, a specific PDE4 inhibitor. Proliferation of several HTLV-I+ T-cell lines, PBMC-PHA, and Jurkat cells was inhibited differentially by forskolin (which activates adenylyl cyclase), the selective PDE inhibitors cilostamide and rolipram, and the nonselective PDE inhibitors pentoxifylline and isobutyl methylxanthine. These results suggest that PDE4 isoforms may be functionally up-regulated in HTLV-I+ T-cells and may contribute to the virus-induced proliferation, and that PDEs could be therapeutic targets in immune/inflammatory and neoplastic diseases.
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PMID:Cyclic nucleotide phosphodiesterases (PDE) 3 and 4 in normal, malignant, and HTLV-I transformed human lymphocytes. 1050 46

HTLV-I is considered to be a virus of low morbidity, since the principal diseases associated with this viral infection, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL), are observed in less than 5% of infected individuals. Urinary symptoms are frequent in patients with myelopathy and consist principally of nocturia, frequency, urgency, and urinary incontinence; however, the importance of these dysfunctions and their correlation with myelopathy is still to be fully clarified. This review gives particular emphasis to the high frequency of urinary and sexual complaints not only in patients with myelopathy but also in individuals considered to be HTLV-I carriers. Detrusor overactivity and bladder-sphincter dyssynergia are the most common urodynamic findings. The fact that urinary complaints and urodynamic parameters reported in individuals considered to be carriers are similar to those detected in patients with myelopathy supports the hypothesis that urinary disorders may represent an oligosymptomatic form of HAM/TSP. Erectile dysfunction is frequently observed in HTLV-I-infected patients with or without myelopathy. Urinary tract infections are also highly prevalent in these patients. Despite the lack of an effective treatment for myelopathy, the use of anticholinergic drugs and phosphodiesterase type 5 (PDE5) inhibitors may improve urinary complaints and erectile dysfunction in these patients.
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PMID:Urinary and sexual manifestations of patients infected by HTLV-I. 1750 5