Acta Pharmaceutica, Vol. 65 No. 2, 2015.
Short communication, Note
https://doi.org/10.1515/acph-2015-0016
The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor
OSAMU SUZUKI
; Biological Research, Laboratories III; Department of Bioengineering, Tokyo Institute of Technology, Kanagawa 226-8501, Japan
TAIJI GOTO
; Lead Discovery & Optimization Research, Laboratories II, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan
TOSHIHARU YOSHINO
; Lead Discovery & Optimization Research, Laboratories II, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan
SATOSHI NAKAMURA
; Department of Bioengineering, Tokyo Institute of Technology, Kanagawa 226-8501, Japan
HIROAKI MAEDA
; Biological Research, Laboratories III
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 inhibited TNF-α production by LPS-stimulated human mononuclear cells in a similar manner. 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.
Keywords
phosphodiesterase 4B; phosphodiesterase 4D; mononuclear cells; neutrophils
Hrčak ID:
128995
URI
Publication date:
30.6.2015.
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