J Pharmacol Exp Ther 2002,
PMID: 11907182
Corbel, Marianne; Germain, Noëlla; Lanchou, Jérôme; Molet, Sophie; R e Silva, Patricia M; Martins, Marco A; Boichot, Elisabeth; Lagente, Vincent
Matrix metalloproteinases (MMPs) and transforming growth factor (TGF)-beta are involved in airway remodeling associated with the inflammatory process. In this study, we investigated the effect of RP 73-401 (piclamilast), a selective phosphodiesterase-4 inhibitor, on MMP-9 activity and TGF-beta production in two murine models of acute inflammation. In the first model, the lipopolysaccharide (LPS)-induced increase in neutrophils, MMP-9 activity, and tumor necrosis factor (TNF)-alpha and TGF-beta release in bronchoalveolar lavage (BAL) was significantly reduced by RP 73-401 pretreatment. In contrast, the BAL interleukin (IL)-10 level was decreased by LPS but restored by RP 73-401. IL-10 administration in LPS-exposed mice elicited a significant reduction in BAL neutrophilia, MMP-9 activity, and TNF-alpha release but not in TGF-beta production. In the second model, RP 73-401 inhibited BAL neutrophils but not MMP-9 activity and TGF-beta production that were induced by intranasal TNF-alpha. We demonstrated that RP 73-401 might modulate the expression of airway remodeling-associated mediators such as MMP-9 and TGF-beta and that this effect seemed to be at least partially mediated by the balance between TNF-alpha and IL-10.
Diseases/Pathways annotated by Medline MESH: Lung Diseases
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Text Mining Data
tumor necrosis factor (TNF)-alpha → lipopolysaccharide (LPS): "
In the first model, the
lipopolysaccharide (LPS) induced increase in neutrophils, MMP-9 activity, and
tumor necrosis factor (TNF)-alpha and TGF-beta release in bronchoalveolar lavage (BAL) was significantly reduced by RP 73-401 pretreatment
"
MMP-9 → lipopolysaccharide (LPS): "
In the first model, the lipopolysaccharide (LPS) induced increase in neutrophils, MMP-9 activity, and tumor necrosis factor (TNF)-alpha and TGF-beta release in bronchoalveolar lavage (BAL) was significantly reduced by RP 73-401 pretreatment
"
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