title: 15-Deoxy-Delta12,14-prostaglandin J2 regulates endogenous Cot MAPK kinase kinase 1 activity induced by lipopolysaccharide.
abstract: Cot is a MAPK kinase kinase that has been implicated in cellular activation and proliferation. Here, we show that the addition of lipopolysaccharide (LPS) to RAW264 macrophages induces a 10-fold increase of endogenous Cot activity, measured as MAPK kinase kinase 1 activity. Taxol, but not phorbol 12-myristate 13-acetate (PMA), induces a similar activation of Cot. A tyrosine kinase activity is involved in Cot activation by LPS. 15-Deoxy-Delta12,14-prostaglandin J2, but not rosiglitazone, blocks Cot activation by LPS. Furthermore, 15-deoxy-Delta12,14-prostaglandin J2 also inhibited the LPS-induced Cot in vitro. However, 15-deoxy-Delta12,14-prostaglandin J2 does not inhibit MAPK kinase 1 or ERK1/ERK2 activation/phosphorylation induced by PMA and mediated by c-Raf. Considering these data, we propose that the inhibition of LPS-induced Cot activation is one mechanism by which 15-deoxy-Delta12,14-prostaglandin J2 acts as an anti-inflammatory.
authors.affiliation: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Facultad Medicina Universidad Autónoma de Madrid, Arturo Duperier 4, 28029 Madrid, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Caivano
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodriguez
authors.forename: Philip
authors.initials: P
authors.lastname: Cohen
authors.forename: Susana
authors.initials: S
authors.lastname: Alemany
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015153:Blotting, Western; D002273:Carcinogens; D002455:Cell Division; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D007211:Indoles / Q000494:pharmacology; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D011233:Precipitin Tests; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology*; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077154:Rosiglitazone; D013755:Tetradecanoylphorbol Acetate; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D007211:Indoles; D008024:Ligands; D008070:Lipopolysaccharides; D008301:Maleimides; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011505:Protein-Tyrosine Kinases; D019908:Proto-Oncogene Proteins c-raf; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C489843:Map3k8 protein, mouse; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate; D017239:Paclitaxel; D015230:Prostaglandin D2