Effects of PDE4 inhibitors on lipopolysaccharide-induced priming of superoxide anion production from human mononuclear cells
Aims: Phosphodiesterase 4 (PDE4) inhibitors have been described as potent anti-inflammatory compounds, involving an increase in intracellular levels of cyclic 39 ,59 -adenosine monophosphate (AMP). The aim of this study was to compare the effects of selective PDE4 inhibitors, rolipram and RP 73-401...
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Published in | Mediators of Inflammation Vol. 2001; pp. 117 - 123 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Hindawi Limiteds
01.12.2001
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Subjects | |
Online Access | Get full text |
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Summary: | Aims: Phosphodiesterase 4 (PDE4) inhibitors have been described as potent anti-inflammatory compounds, involving an increase in intracellular levels of cyclic 39 ,59 -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^(-8) to 10^(-5) M) induced significant reductions of fMLP-induced superoxide anion production in cells incubated with or without LPS. The db-cAMP (10^(-5) to 10^(-3) 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. |
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ISSN: | 0962-9351 |
DOI: | 10.1080/09629350120072680 |