Basic and Clinical ImmunologyRole of activator protein 1, nuclear factor-κB, and nuclear factor of activated T cells in IgE receptor-mediated cytokine expression in mature human mast cells☆,☆☆
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Isolation and culture of human intestinal mast cells
Human intestinal mast cells were isolated from surgical tissue specimens (macroscopically normal border sections free of tumor cells, as determined by means of histologic examination of the tissue) derived from patients who underwent bowel resection because of cancer. Permission to conduct the study was obtained from the local ethical committee of the Medical School of Hannover. The methods of mechanical and enzymatic tissue dispersion yielding single-cell preparations containing 4% ± 2% (mean
NF-κB, c-Fos, and c-Jun are activated after FcϵRI cross-linking in human intestinal mast cells
FcϵRI-mediated cytokine production in mast cells is regulated at the transcriptional level.4, 6, 19 The transcription factors NF-κB and AP-1 are known to regulate the expression of multiple inflammatory genes.20 Mast cells were treated with 100 ng/mL mAb 29C6 and centrifugated on slides to access activation of NF-κB in response to FcϵRI cross-linking. Immunostaining of the cells revealed a translocation of NF-κB into the nucleus in response to FcϵRI stimulation (Fig 1, A ).
DISCUSSION
Mast cells play a central role in inflammatory and particularly in allergic reactions. Recently, we reported that FcϵRI cross-linking induces the expression of multiple cytokines in mature human mast cells isolated from intestinal mucosa.6 Several transcription factors are known to be involved in allergic inflammation, including NF-κB, AP-1, and NF-AT.20 In this study we show that NF-κB and AP-1 become activated in response to FcϵRI cross-linking in human intestinal mast cells and that the
Acknowledgements
We thank Antje Radke, Nicole Steegmann, Birgit Hegemann, and Gisela Weier for excellent technical assistance.
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Supported by the Deutsche Forschungsgemeinschaft (SFB621-A8).
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Reprint requests: Axel Lorentz, PhD, Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, D-30623 Hannover, Germany.