Effects of PDE4 inhibitors on lipopolysaccharide-induced priming of superoxide anion production from human mononuclear cellsReport as inadecuate




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Mediators of Inflammation - Volume 10 2001, Issue 3, Pages 117-123



INSERM U456, Laboratoire de Pharmacodynamie et de Pharmacologie Moléculaire, Faculté des Sciences, Pharmaceutiques et Biologiques, Université de Rennes 1, 2 avenue du Professeur Léon Bernard, Rennes cedex, Rennes 35043, France

Service de Pneumologie, Hôpital de Pontchaillou, CHU de Rennes, Rennes 35000, France



Copyright © 2001 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aims: Phosphodiesterase 4 PDE4 inhibitors have been described as potent anti-inflammatory compounds, involving an increase in intracellular levels of cyclic 3-,5-adenosine monophosphate AMP. The aim of this study was to compare the effects of selective PDE4 inhibitors, rolipram and RP 73-401 with the cell permeable analogue of cyclic AMP, dibutyryl-cyclic AMP db-cAMP and the anti-inflammatory cytokine interleukin-10 IL-10 on superoxide anion production from peripheral blood mononuclear cells preincubated with lipopolysaccharide LPS.

Major findings: We report that, after incubation of the cells with LPS, a large increase in superoxide anion production was observed. Rolipram or RP 73-401 10

to 10

M induced significant reductions of fMLP-induced superoxide anion production in cells incubated with or without LPS. The db-cAMP 10

to 10

M also elicited dose-dependent inhibitions of the fMLP-induced superoxide anion production. In contrast, IL-10 1 or 10 ng-ml did not elicit a reduction in fMLP-induced superoxide anion production in both conditions.

Principal conclusion: These results suggest that the inhibitory activity of PDE4 inhibitors on fMLPinduced production of superoxide anion production is mediated by db-cAMP rather than IL-10.





Author: Noëlla Germain, Marianne Corbel, Chantal Belleguic, Elisabeth Boichot, and Vincent Lagente

Source: https://www.hindawi.com/



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