NF-κB and TNF-α: A Positive Autocrine Loop in Human Lung Mast Cells?

摘要: The generation of cytokines, particularly TNF-alpha, by mast cells is crucial for the initiation allergic response. A key transcription factor involved in synthesis TNF-alpha NF-kappaB. Using a mAb specific activated form NF-kappaB, immunocytochemistry, confocal microscopy, and gel shift assays have been used conjunction to localize this human lung study its activation. Activation with stem cell (10 ng/ml) anti-IgE (1 micro g/ml) induced maximal activation NF-kappaB at 4 2 h, respectively. In contrast, (5 occurred within 15 min. Parallel falls IkappaB were demonstrated. Confocal microscopy demonstrated localization nuclei cells. was verified using assay. supershift assay showed be composed primarily p50 smaller amounts p65. No interaction Abs Rel-A, c-Rel, Rel-B, p52 seen. Immunocytochemistry ELISAs stored released into extracellular environment following possible participation generated investigated blocking Ab TNF-alpha. reduced >50%, suggesting that release preformed cell-associated acts as positive autocrine feedback signal augment production further cytokine, including GM-CSF IL-8.