Effects of PDE4 inhibitors on lipopolysaccharide-induced priming of superoxide anion production from human mononuclear cells

Noëlla Germain ； Marianne Corbel ； Chantal Belleguic ； Elisabeth Boichot ； Vincent Lagente

《Mediators of Inflammation》 2001卷 (2001/12) Pp. 117-123

https://doi.org/10.1080/09629350120072680

摘要

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.

關鍵字

Cyclic AMP ； Interleukin 10 ； Lipopolysaccharide ； Mononuclear cells ； Phosphodiesterase inhibitors ； TNF-α