دورية أكاديمية
Regulatory roles of adenylate cyclase and cyclic nucleotide phosphodiesterases 1 and 4 in interleukin-13 production by activated human T cells.
| العنوان: | Regulatory roles of adenylate cyclase and cyclic nucleotide phosphodiesterases 1 and 4 in interleukin-13 production by activated human T cells. |
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| المؤلفون: | Kanda N; Department of Dermatology, Teikyo University, School of Medicine, 11-1, Kaga 2, Itabashi-Ku, Tokyo 173-8605, Japan. nmk@med.teikyo-u.ac.jp, Watanabe S |
| المصدر: | Biochemical pharmacology [Biochem Pharmacol] 2001 Aug 15; Vol. 62 (4), pp. 495-507. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print Cited Medium: Print ISSN: 0006-2952 (Print) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| مواضيع طبية MeSH: | 3',5'-Cyclic-AMP Phosphodiesterases/*metabolism , Adenylyl Cyclases/*metabolism , Interleukin-13/*metabolism , Lymphocyte Activation/*physiology , T-Lymphocytes/*enzymology, 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors ; Adenylyl Cyclase Inhibitors ; Adult ; Antibodies/pharmacology ; CD28 Antigens/immunology ; CD3 Complex/immunology ; Cyclic AMP/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 1 ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Enzyme Inhibitors/pharmacology ; Female ; Humans ; In Vitro Techniques ; Isoenzymes/metabolism ; Kinetics ; Male ; Phytohemagglutinins/pharmacology ; T-Lymphocytes/drug effects ; T-Lymphocytes/metabolism ; Time Factors |
| مستخلص: | We studied the activities of 3',5'-adenosine-cyclic monophosphate (cAMP)- synthesizing adenylate cyclase (AC) and cAMP-hydrolyzing cyclic nucleotide phosphodiesterase (PDE) in phytohemagglutinin (PHA)- or anti-CD3 plus anti-CD28-stimulated human T cells, and examined their roles in interleukin-13 (IL-13) production. The AC inhibitor MDL 12,330A [cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine hydrochloride] completely blocked PHA- or anti-CD3/CD28-induced IL-13 production. The PDE 1 inhibitor 8-methoxymethyl-3-isobutyl-1-methylxanthine or the PDE4 inhibitor rolipram partially inhibited IL-13 production, and the addition of both resulted in 100 or 85% inhibition in PHA- or anti-CD3/CD28-stimulated T cells, respectively. AC in T cells was transiently activated 5 min after stimuli, followed by the transient activation of PDE4 at 30 min. PDE1 activity, undetectable in resting T cells, was detected 3 hr after stimuli, and then increased gradually. Although PDE1-, 2-, 3-, and 4-independent PDE activity was low (< or = 15% of total), it began to increase 3 hr after anti-CD3/CD28; the increase was blocked by PDE7 antisense oligonucleotide, and such an increase was not induced by PHA. PHA or anti-CD3/CD28 induced PDE1B mRNA expression, undetectable in resting T cells. PDE4 mRNA level in T cells was not altered by either stimulus. PDE7 mRNA expression was detected in resting T cells, and was enhanced by anti-CD3/CD28, but not by PHA. The cAMP level of T cells increased 5 min after stimuli, returned to the basal level at 2 hr, and then continued to decrease. These results suggest that PHA or anti-CD3/CD28 initially (< or = 5 min) increases cAMP in T cells via AC, then reverses the increase via PDE4 (< or = 2 hr), and in the later phase (> 2 hr) further decreases cAMP via PDE1. Both the time-dependent increase and decrease of cAMP may be required for IL-13 production. |
| التعليقات: | Erratum in: Biochem Pharmacol 2001 Dec 15;62(12):1758. |
| المشرفين على المادة: | 0 (Adenylyl Cyclase Inhibitors) 0 (Antibodies) 0 (CD28 Antigens) 0 (CD3 Complex) 0 (Enzyme Inhibitors) 0 (Interleukin-13) 0 (Isoenzymes) 0 (Phytohemagglutinins) E0399OZS9N (Cyclic AMP) EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases) EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 1) EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4) EC 4.6.1.1 (Adenylyl Cyclases) |
| تواريخ الأحداث: | Date Created: 20010713 Date Completed: 20010719 Latest Revision: 20190623 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/s0006-2952(01)00688-8 |
| PMID: | 11448460 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0006-2952 |
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| DOI: | 10.1016/s0006-2952(01)00688-8 |