Inflammation Research

, Volume 53, Issue 1, pp 31–37

KF19514, a phosphodiesterase 4 and 1 inhibitor, inhibits TNF-α-induced GM-CSF production by a human bronchial epithelial cell line via inhibition of PDE4

Original Paper
  • 85 Downloads

Abstract

Objective and design: Bronchial epithelium plays an important role in the regulation of inflammatory reactions in the airways. We investigated the effect of KF19514, a phosphodiesterase (PDE) 4 and 1 inhibitor, on granulocyte-macrophage colony-stimulating factor (GM-CSF) production by a human bronchial epithelial cell line, BEAS-2B.

Methods: BEAS-2B cells were stimulated with the tumor necrosis factor-α (TNF-α) and various concentrations of test agents for 48 h. Supernatants were assayed for GM-CSF by using an enzyme-linked immunosorbent assay (ELISA). In addition, intracellular cyclic AMP (cAMP) levels were measured in the presence of various agents.

Results: KF19514 significantly inhibited the release of GM-CSF by BEAS-2B cells in a concentration-dependent manner. The other PDE4 inhibitors and cAMP-elevating agents also inhibited the GM-CSF production. In the BEAS-2B cells, KF19514 and PDE4 inhibitors concentration-dependently increased intracellular cAMP levels. The inhibitory effect of KF19514 on the GM-CSF production was significantly reduced by a cAMP-dependent protein kinase A (PKA) inhibitor, H89. On the other hand, other PDE isozyme inhibitors did not inhibit the GM-CSF production by BEAS-2B cells, and did not elevate the intracellular cAMP levels.

Conclusions: These results indicate that KF19514 and PDE4 inhibitors reduce TNF-α-induced GM-CSF production of BEAS-2B cells via a cAMP-dependent pathway. PDE4 may be a possible target for the regulation of cytokine production in epithelial cells.

BEAS-2B GM-CSF KF19514 PDE4 inhibitor Cyclic-AMP 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Birkhäuser-Verlag Basel 2004

Authors and Affiliations

  1. 1.Pharmaceutical Research InstituteKyowa Hakko Kogyo Co., Ltd.ShizuokaJapan

Personalised recommendations