title: Human endotoxemia activates p38 MAP kinase and p42/44 MAP kinase, but not c-Jun N-terminal kinase.
abstract: BACKGROUND
  All three major members of the MAPK family (i.e., p38 MAPK, p42/p44 MAPK, and c-Jun N terminal kinase (JNK)) have been shown to control cellular responses to inflammation in vitro. Therefore these kinases have been designated suitable targets for anti-inflammatory therapy. However, the extent to which these kinases are actually activated during inflammation in humans in vivo has not been investigated. We employed experimental human endotoxemia, a model of systemic inflammation, to address this question.
  
  
  METHODS
  Male volunteers were intravenously infused with 4 ng/kg bw lipopolysaccharide (LPS). Directly before LPS infusion and up to 24 h thereafter, activation of p38 MAPK, p42/p44 MAPK and JNK was assessed in peripheral blood, using Western blot and in vitro kinase assays.
  
  
  RESULTS
  We observed that LPS induced a strong but transient phosphorylation and activation of p38 MAPK and p42/p44 MAPK, maximal activity being reached after 1 hr of LPS infusion. Strikingly, no JNK phosphorylation or activation was detected under these circumstances.
  
  
  CONCLUSIONS
  These results suggest that both inhibitors of p38 MAPK and p42/p44 MAPK but not JNK are potentially useful for anti-inflammatory therapy.
authors.affiliation: Department of Experimental Internal Medicine, Academic Medical Center, The Netherlands. B.vandenBlink@amc.uva.nl
authors.forename: B
authors.initials: B
authors.lastname: van den Blink
authors.forename: J
authors.initials: J
authors.lastname: Branger
authors.forename: S
authors.initials: S
authors.lastname: Weijer
authors.forename: S H
authors.initials: SH
authors.lastname: Deventer
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: M P
authors.initials: MP
authors.lastname: Peppelenbosch
mesh_terms: D000328:Adult; D015153:Blotting, Western; D019446:Endotoxemia / Q000097:blood*; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007962:Leukocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D019950:Mitogen-Activated Protein Kinase 1 / Q000097:blood*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000097:blood*; D010766:Phosphorylation; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D008070:Lipopolysaccharides; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases