Differential involvement of ceramide in TNFalpha-mediated activation of NF-kappaB in primary human keratinocytes and HaCaT keratinocytes.
The involvement of ceramide signaling in tumor necrosis factor alpha (TNFalpha) mediated nuclear transcription factor kappa B (NF-kappaB) activation was studied. The cell response modifier ceramide has been shown to modulate apoptosis, cell differentiation and cell proliferation in different cell populations. Sphingomyelin hydrolysis is one pathway generating intracellular ceramide increase. Previously, we could show that TNFalpha induces a ceramide increase in primary human keratinocytes and HaCaT keratinocytes and consequently apoptosis was initiated. It is well known that TNFalpha activates the transcription factor NF-kappaB, but there have been controversial reports on the role of ceramide in TNFalpha-mediated NF-kappaB activation. Here we show by different lines of experimental evidence that TNFalpha is a strong inducer of NF-kappaB in both cell types, whereas C2-ceramide failed to activate NF-kappaB in HaCaT keratinocytes in contrast to primary keratinocytes.
Departement of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstrasse 60-62, D-14195 Berlin-Dahlem, Germany.
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D000577:Amides / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009636:Norbornanes; D010457:Peptidoglycan / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000577:Amides; D001952:Bridged-Ring Compounds; D002518:Ceramides; D020672:I-kappa B Proteins; C421619:N-(1-(4-nitrophenyl)-1,3-dihydroxyprop-2-yl)tetradecanamide; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009636:Norbornanes; D010457:Peptidoglycan; D011412:Propanolamines; D013859:Thiocarbamates; D013871:Thiones; D014409:Tumor Necrosis Factor-alpha; C029323:pneumococcal purpura-producing principle; D000072000:NF-KappaB Inhibitor alpha; C046498:tricyclodecane-9-yl-xanthogenate