title: Activation and translocation of p38 mitogen-activated protein kinase after stimulation of monocytes with contact sensitizers.
abstract: Recently we described the induction of tyrosine phosphorylation by contact sensitizers as an early molecular event during the activation of antigen- presenting cells. In this study, the role of the p38 mitogen-activated protein kinase for the activation of human monocytes after exposure to four structurally unrelated contact sensitizers was analyzed in comparison with the irritant benzalkonium chloride and an inductor of oxidative stress (H2O2) using immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay techniques. Bio chemical analysis revealed a translocation of p38 from the cytoplasm to the detergent-resistant cell fraction only upon stimulation with contact sensitizers. The activity of p38 was studied by quantification of its phosphorylated active form with a specific antibody and by kinase assay. Although all stimulants used in this study led to the activation of p38, a translocation to the detergent-resistant fraction as well phosphorylation of the mitogen-activated protein kinase dependent transcription factor Elk-1 was induced only by contact sensitizers. Evidence for a functional relevance of mitogen-activated protein kinase activation was provided by measurement of the hapten-induced production of the proinflammatory cytokine interleukin-1beta. Its release was inhibited by blocking p38-mediated signaling using the imidazole compounds SB203580 and SB202190. These data show that contact sensitizers are strong activators of the p38 mitogen-activated protein kinase. Although activation of this stress-associated pathway has been reported for many other stimuli, a unique translocation of p38 from the cytoplasm to the detergent-resistant fraction seems to be a specific event during hapten-induced activation of antigen-presenting cells.
authors.affiliation: Department of Dermatology, University of Mainz, Langenbeckstrasse 1, D-55131 Mainz, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Brand
authors.forename: Sibylle
authors.initials: S
authors.lastname: Plochmann
authors.forename: Elke
authors.initials: E
authors.lastname: Valk
authors.forename: Sabine
authors.initials: S
authors.lastname: Zahn
authors.forename: Joachim
authors.initials: J
authors.lastname: Saloga
authors.forename: Jürgen
authors.initials: J
authors.lastname: Knop
authors.forename: Detlef
authors.initials: D
authors.lastname: Becker
mesh_terms: D001548:Benzalkonium Compounds / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003593:Cytoplasm / Q000201:enzymology; D004268:DNA-Binding Proteins; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006241:Haptens / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D007509:Irritants / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D001548:Benzalkonium Compounds; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D004791:Enzyme Inhibitors; D006241:Haptens; D007093:Imidazoles; D007375:Interleukin-1; D007509:Irritants; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole