Document 0440
 DOCN  M9650440
 TI    Effect of phosphodiesterase inhibition on IL-4 and IL-5 production of
       the murine TH2-type T cell clone D10.G4.1.
 DT    9605
 AU    Schmidt J; Hatzelmann A; Fleissner S; Heimann-Weitschat I; Lindstaedt R;
       Szelenyi I; ASTA Medica AG, Department of Pharmacology, Frankfurt/Main,;
       Germany.
 SO    Immunopharmacology. 1995 Sep;30(3):191-8. Unique Identifier : AIDSLINE
       MED/96128551
 AB    The effect of various phosphodiesterase (PDE) inhibitors on anti-CD3
       induced interleukin-(IL)-4 and IL-5 production of the murine T helper
       cell clone of type 2 phenotype D10.G4.1 (D10) has been investigated in
       vitro. D10 cells were incubated in the presence of drugs and anti-CD3
       mAb for 16 h before measurement of cytokines in the cell supernatants by
       ELISA. Whereas all PDE inhibitors tested exerted minimal effects on
       anti-CD3 induced IL-4 production, a marked increase in IL-5 production
       by the non-selective PDE inhibitors IBMX, theophylline and enprofylline
       was observed. The action of these non-selective PDE inhibitors was
       mimicked by the PDE IV-selective inhibitor rolipram and in part by the
       PDE III-selective inhibitors motapizone and milrinone, whereas the PDE
       V-selective inhibitor zaprinast was inactive. Rolipram and motapizone
       enhanced IL-5 production in a synergistic fashion. In support of the
       functional importance of PDE III and IV for IL-5 synthesis in intact
       murine D10 cells, we have found PDE III and IV to be the predominant
       isoenzyme activities in corresponding cell lysates. The stimulatory
       effect of rolipram on IL-5 production was almost totally reversed by the
       protein kinase A inhibitor KT-5720. In addition, the membrane-permeable
       cAMP analogue 8-bromo-cAMP mimicked the stimulatory effect of PDE
       inhibitors on IL-5 production while leaving IL-4 levels unaffected. Both
       results support the view that the action of the PDE inhibitors on murine
       D10 cells is mediated via an elevation of intracellular cAMP.
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY  Cells, Cultured  Clone Cells
       Cyclic AMP-Dependent Protein Kinases/ANTAGONISTS & INHIB/  PHYSIOLOGY
       Interleukin-4/*BIOSYNTHESIS  Interleukin-5/*BIOSYNTHESIS
       Isoenzymes/ANTAGONISTS & INHIB  Mice  Mice, Inbred AKR
       Phosphodiesterase Inhibitors/*PHARMACOLOGY  Pyridazines/PHARMACOLOGY
       Th2 Cells/*DRUG EFFECTS/ENZYMOLOGY/METABOLISM  8-Bromo Cyclic Adenosine
       Monophosphate/PHARMACOLOGY  JOURNAL ARTICLE

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