Acta Pharm. 65 (2015) 191-197
The role of phosphodiesterase 4B in IL-8/LTB4-induced human neutrophil chemotaxis evaluated with a phosphodiesterase 4B inhibitor
OSAMU SUZUKI, TAIJI GOTO, TOSHIHARU YOSHINO, SATOSHI NAKAMURA and HIROAKI MAEDA
1 Biological Research, Laboratories III
2 Lead Discovery & Optimization Research, Laboratories II, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan
3 Department of Bioengineering, Tokyo Institute of Technology, Kanagawa 226-8501, Japan
Accepted December 22, 2014
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
† Present address: Cardiovascular-Metabolics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan