Human endotoxemia activates p38 MAP kinase and p42/44 MAP kinase, but not c-Jun N-terminal kinase

Mol Med. 2001 Nov;7(11):755-60.


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.

Materials and 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.

MeSH terms

  • Adult
  • Blotting, Western
  • Endotoxemia / blood*
  • Enzyme Activation
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Leukocytes / metabolism
  • Lipopolysaccharides / administration & dosage
  • Mitogen-Activated Protein Kinase 1 / blood*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / blood*
  • Phosphorylation
  • Signal Transduction*
  • p38 Mitogen-Activated Protein Kinases


  • Lipopolysaccharides
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases