<abstract xmlns="http://www.w3.org/1999/xhtml">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.</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.

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

Department of Bioengineering, Tokyo Institute of Technology, Kanagawa 226-8501, Japan

Cardiovascular-Metabolics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan

Lead Discovery and Optimization Research Laboratories II Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The role of phosphodiesterase 4B in IL-8/LTB-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...

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

Publicado en línea: 23 may 2015

Páginas: 191 - 197

Aceptado: 22 dic 2014

DOI: https://doi.org/10.1515/acph-2015-0016

© by Osamu Suzuki

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.