JAK/STAT pathways are not involved in the direct activation of antigen-presenting cells by contact sensitizers.
JAK/STAT pathways are described as the major mechanisms by which cytokine receptors transduce intracellular signals. The signalling mechanisms in antigen-presenting cells (APC) in the sensitization phase of contact hypersensitivity are poorly understood. The aim of this study was to clarify whether well-established JAK/STAT signalling pathways might be activated directly by contact sensitizers as described previously for tyrosine kinases and some MAP kinases. As a model of epidermal APC, human monocytes and human monocyte-derived dendritic cells were stimulated with the structurally unrelated contact sensitizers MCI/MI, thimerosal, TNCB and formaldehyde. The phosphorylation states of the transcription factors STAT1, STAT3, STAT4, STAT5 and STAT6 were determined by Western blot analysis using phosphospecific antibodies. In contrast to the positive controls performed with the cytokines IFN-gamma, IL-10, IFN-alpha, GM-CSF and IL-4, no significant increase in the phosphorylation of STAT molecules was recognized in hapten-treated cells. These results suggest that contact allergens do not directly activate common JAK/STAT pathways. Therefore the activation of APC in the early sensitization phase of contact hypersensitivity by haptens does not involve signals normally delivered by JAK-associated cytokine receptors.
Department of Dermatology, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. valk@hautklinik.klinik.uni-mainz.de
Elke
E
Valk
Sabine
S
Zahn
Jürgen
J
Knop
Detlef
D
Becker
D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006241:Haptens / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases; D008894:Milk Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
D016207:Cytokines; D004268:DNA-Binding Proteins; D006241:Haptens; D008894:Milk Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases