The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor

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 inhibit...

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Main Authors: Suzuki Osamu, Goto Taiji, Yoshino Toshiharu, Nakamura Satoshi, Maeda Hiroaki
Format: Article
Language:English
Published: Sciendo 2015-06-01
Series:Acta Pharmaceutica
Subjects:
Online Access:https://doi.org/10.1515/acph-2015-0016
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author Suzuki Osamu
Goto Taiji
Yoshino Toshiharu
Nakamura Satoshi
Maeda Hiroaki
author_facet Suzuki Osamu
Goto Taiji
Yoshino Toshiharu
Nakamura Satoshi
Maeda Hiroaki
author_sort Suzuki Osamu
collection DOAJ
description 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.
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spelling doaj.art-c007b450b8074eb9b7f09096d72f58a92022-12-21T22:07:55ZengSciendoActa Pharmaceutica1846-95582015-06-0165219119710.1515/acph-2015-0016acph-2015-0016The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitorSuzuki Osamu0Goto Taiji1Yoshino Toshiharu2Nakamura Satoshi3Maeda Hiroaki4Biological Research Laboratories IIILead Discovery and Optimization Research Laboratories II Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanLead Discovery and Optimization Research Laboratories II Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanDepartment of Bioengineering, Tokyo Institute of Technology, Kanagawa 226-8501, JapanBiological Research Laboratories IIIPDE4B 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.https://doi.org/10.1515/acph-2015-0016phosphodiesterase 4bphosphodiesterase 4dmononuclear cellsneutrophils
spellingShingle Suzuki Osamu
Goto Taiji
Yoshino Toshiharu
Nakamura Satoshi
Maeda Hiroaki
The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor
Acta Pharmaceutica
phosphodiesterase 4b
phosphodiesterase 4d
mononuclear cells
neutrophils
title The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor
title_full The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor
title_fullStr The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor
title_full_unstemmed The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor
title_short The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor
title_sort role of phosphodiesterase 4b in il 8 ltb4 induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4b inhibitor
topic phosphodiesterase 4b
phosphodiesterase 4d
mononuclear cells
neutrophils
url https://doi.org/10.1515/acph-2015-0016
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