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 kappaB (NF-kappaB)-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-kappaB activate the production of reactive oxygen species and three mitogen-activated 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 alpha (TNF-alpha), IL-6 and nitrite.
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Cécile
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Unité 365 INSERM 'Interférons et Cytokines', Institut Curie, Section de Recherche, Pavillon Pasteur, 26 rue d'Ulm, F-75248 Paris 05, France.
Wietzerbin
Juana
J
D019797:3-Iodobenzylguanidine / Q000494:pharmacology; D020727:ADP-Ribosylation Factors / Q000037:antagonists & inhibitors*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced; D007375:Interleukin-1 / Q000032:analysis; D008070:Lipopolysaccharides / Q000032:analysis; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D009536:Niacinamide / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases
D000975:Antioxidants; D001549:Benzamides; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C066229:prolinedithiocarbamate; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D019797:3-Iodobenzylguanidine; C025160:3-aminobenzamide; D011392:Proline; D011494:Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020727:ADP-Ribosylation Factors