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C. Le Page, J. Wietzerbin

Modulation of the Activation of Extracellular Signal-Regulated Kinase (ERK) and the Production of Inflammatory Mediators by ADP-Ribosylation Inhibitors

ADP-ribosylation is involved in nuclear factor ?B (NF-?B)-dependent gene expression induced by lipopolysaccharide in murine macrophages. Here we have investigated the mechanism by which ADP-ribosylation inhibitors block signaling pathways induced in macrophages. In RAW264.7 macrophages the inducers of NF-?B activate the production of reactive oxygen species and three mitogenactivated protein kinases (MAPK), the extracellular signal regulated kinase (ERK), the c-jun N-terminal kinase/stress-activated protein kinase (JNK), and p38. We demonstrate that ADP-ribosylation inhibitors specifically inhibit ERK MAPK activation and reduce the release of inflammatory mediators such as tumor necrosis factor ? (TNF-?), IL-6 and nitrite.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 384, 11/2003
Pages: 1509 - 1513

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