title: The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor.
abstract: PDE4B was previously shown to be a dominant PDE4 subtype of neutrophils. However, its physiological role in the neutrophil function has not been evaluated. In this study, the inhibitory effects of a phosphodiesterase 4B (PDE4B)- selective inhibitor (compound A) and subtype non-selective PDE4 inhibitors (roflumilast and cilomilast) were evaluated in human peripheral blood cells. Compound A, roflumilast and cilomilast in a similar manner inhibited TNF-α production by LPS-stimulated human mononuclear cells. However, the inhibitory effect of compound A on IL-8 or LTB4-induced chemotactic response of neutrophils was modest even at the highest concentration (10 μmol L(-1)), whereas roflumilast and cilomilast inhibited IL-8 or LTB4-induced neutrophil chemotaxis. Our results suggest that PDE4B does not play an important role during the chemotactic response of human neutrophils.
authors.forename: Osamu
authors.initials: O
authors.lastname: Suzuki
authors.forename: Taĳi
authors.initials: T
authors.lastname: Goto
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yoshino
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Maeda
mesh_terms: D000328:Adult; D000631:Aminopyridines / Q000008:administration & dosage / Q000494:pharmacology; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000187:drug effects* / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology; D003521:Cyclopropanes / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D007975:Leukotriene B4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003509:Cyclohexanecarboxylic Acids; D003521:Cyclopropanes; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009570:Nitriles; D058988:Phosphodiesterase 4 Inhibitors; D014409:Tumor Necrosis Factor-alpha; C424423:Roflumilast; D007975:Leukotriene B4; C433247:Cilomilast; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4