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Int. J. Mol. Sci. 2018, 19(11), 3511; https://doi.org/10.3390/ijms19113511

Dexamethasone Inhibits Synergistic Induction of PDE4B Expression by Roflumilast and Bacterium NTHi

1
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
2
Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
*
Author to whom correspondence should be addressed.
Received: 14 October 2018 / Accepted: 6 November 2018 / Published: 8 November 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Phosphodiesterase 4B (PDE4B) plays an important role in inflammation. Recently we have reported that roflumilast as a PDE4-selective inhibitor, synergizes with nontypeable Haemophilus influenzae (NTHi) to up-regulate PDE4B expression in vitro and in vivo. Clinical evidence and our previous results suggest that synergistic induction of PDE4B could be counterproductive for suppressing inflammation or may contribute to tolerance to roflumilast. We thus investigated if dexamethasone inhibits the synergistic induction of PDE4B by roflumilast and NTHi as well as inflammation. Here, dexamethasone markedly suppressed the synergistic induction of PDE4B in human lung epithelial cells and in vivo. We also found that dexamethasone further suppressed NTHi-induced inflammatory response in vitro and in vivo. Moreover, Compound A, as a dissociating non-steroidal glucocorticoid receptor (GR) ligand, inhibited the synergistic induction of PDE4B, thereby suggesting the requirement of dexamethasone-mediated GR activation in the suppression of PDE4B expression. Taken together, our data suggest that dexamethasone may help attenuate inflammation and tolerance through suppressing the PDE4B expression in chronic obstructive pulmonary disease (COPD) patients using roflumilast. View Full-Text
Keywords: dexamethasone; PDE4B; roflumilast; nontypeable Haemophilus influenzae; glucocorticoid receptor dexamethasone; PDE4B; roflumilast; nontypeable Haemophilus influenzae; glucocorticoid receptor
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Lee, B.-C.; Susuki-Miyata, S.; Yan, C.; Li, J.-D. Dexamethasone Inhibits Synergistic Induction of PDE4B Expression by Roflumilast and Bacterium NTHi. Int. J. Mol. Sci. 2018, 19, 3511.

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