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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Sciendo
2015-06-01
|
Series: | Acta Pharmaceutica |
Subjects: | |
Online Access: | https://doi.org/10.1515/acph-2015-0016 |
_version_ | 1818650922143711232 |
---|---|
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. |
first_indexed | 2024-12-17T01:57:54Z |
format | Article |
id | doaj.art-c007b450b8074eb9b7f09096d72f58a9 |
institution | Directory Open Access Journal |
issn | 1846-9558 |
language | English |
last_indexed | 2024-12-17T01:57:54Z |
publishDate | 2015-06-01 |
publisher | Sciendo |
record_format | Article |
series | Acta Pharmaceutica |
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 |
work_keys_str_mv | AT suzukiosamu theroleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor AT gototaiji theroleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor AT yoshinotoshiharu theroleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor AT nakamurasatoshi theroleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor AT maedahiroaki theroleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor AT suzukiosamu roleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor AT gototaiji roleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor AT yoshinotoshiharu roleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor AT nakamurasatoshi roleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor AT maedahiroaki roleofphosphodiesterase4binil8ltb4inducedhumanneutrophilchemotaxisevaluatedwithaphosphodiesterase4binhibitor |