Cyclosporin A-sensitive calcium signaling represses NFkappaB activation in human bronchial epithelial cells and enhances NFkappaB activation in Jurkat T-cells.
Activation of the NFkappaB transcription factor in 16HBE human bronchial epithelial cells was compared with activation of NFkappaB in Jurkat T-cells. An NFkappaB-luciferase reporter gene was activated by phorbol myristyl acetate (PMA) in both cell types. Ionomycin added to PMA (P/I) inhibited NFkappaB activation in epithelial cells and enhanced PMA activation in T-cells. Cyclosporin A (CsA) inhibited calcium signaling in both cell types. Nuclear NFkappaB DNA-binding stimulated with PMA was inhibited with ionomycin in epithelial cells and was enhanced with ionomycin in T-cells; CsA reversed both effects of ionomycin. Cytosolic IkappaB-alpha was regulated identically in both cell types. Thus, calcium activated opposing nuclear signaling pathways in epithelial cells and T-cells. Calcium-mediated repression of NFkappaB in epithelial cells was derepressed by CsA, and this establishes a mechanism through which CsA may exert proinflammatory effects in nonlymphoid cells.
Aoki
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Y
Pulmonary and Critical Care Medicine, Stanford University Medical Center, California 94305-5236, USA.
Kao
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PN
D001483:Base Sequence; D001980:Bronchi / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002461:Cell Line, Transformed; D016572:Cyclosporine / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D007249:Inflammation / Q000209:etiology; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015345:Oligonucleotide Probes / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
D016328:NF-kappa B; D015345:Oligonucleotide Probes; D015759:Ionomycin; D016572:Cyclosporine; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016559:Tacrolimus