DMSO-treated HL60 cells: a model of neutrophil-like cells mainly expressing PDE4B subtype.
The human promyelocytic HL60 cells acquired a neutrophilic phenotype after a 7- to 10-day DMSO treatment. Fc gammaRII was up-regulated. Fc gammaRI was also up-regulated by an additional IFN-gamma treatment. These cells are able to produce O2*- by NADPH oxidase activation in the presence of immune complexes or phorbol-12-myristate-13-acetate (PMA). A change of their PDE4 subtype profile was also observed: PDE4B was the predominant isoenzyme, PDE4D was down-regulated and PDE4A was no longer detectable. Additionally, the more NADPH oxidase was activated by PMA, the less PDE4A was expressed, suggesting that NADPH oxidase activity could be used as a surrogate marker of PDE4A down-regulation. Rolipram and Ariflo (cilomilast), two selective PDE4 inhibitors, dose-dependently inhibited receptor-coupled activation of superoxide. These results suggest that PDE4B is the main subtype involved in regulating superoxide induced by Fc gammaRs activation. Furthermore, these cells, expressing almost exclusively PDE4B subtype, could be useful to identify selective PDE4B inhibitors.
Jacob
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Fresnes Laboratories, Department of Biology, Pfizer Global R&D, 3-9, rue de la Loge, 94265 Fresnes, France. claire.jacob@pfizer.com
Leport
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Szilagyi
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Allen
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JM
Bertrand
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Lagente
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D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D017452:Receptors, IgG; D013481:Superoxides; D019255:NADPH Oxidases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517355:PDE4A protein, human; C517360:PDE4B protein, human; C517376:PDE4D protein, human; D004121:Dimethyl Sulfoxide