Effect of various metals on intercellular adhesion molecule-1 expression and tumour necrosis factor alpha production by normal human keratinocytes

1994 ◽  
Vol 286 (8) ◽  
pp. 466-470 ◽  
Author(s):  
A. Gu�niche ◽  
J. Viac ◽  
G. Lizard ◽  
M. Charveron ◽  
D. Schmitt
Keyword(s):  
Human Keratinocytes ◽  
Tumour Necrosis Factor Alpha ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Alpha Production ◽  
Normal Human Keratinocytes ◽  
Normal Human ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Ambivalent Effects of Tumor Necrosis Factor Alpha on Apoptosis of Malignant and Normal Human Keratinocytes

2021 ◽  
Vol 34 (2) ◽  
pp. 94-102
Author(s):  
Georgios Kokolakis ◽  
Robert Sabat ◽  
Sabine Krüger-Krasagakis ◽  
Jürgen Eberle
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Viability ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Human Keratinocytes ◽  
Necrosis Factor Alpha ◽  
Normal Human Keratinocytes ◽  
Normal Human ◽  
Factor Alpha ◽  
Necrosis Factor

Introduction: Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that may paradoxically induce either apoptosis or cell survival. It mediates its activity through binding of TNF-receptor (TNFR) 1 or 2. TNFR1 is mainly responsible for transmitting apoptotic signals. The activation of apoptotic mechanisms can either be intrinsic (mitochondrial) or extrinsic (death receptors). Death ligands such as TNF-related apoptosis-inducing ligand (TRAIL) specifically induce extrinsic apoptosis, while cytostatic drugs such as 5-fluorouracil (5FU) induce intrinsic apoptosis. Objectives: To investigate the effects of TNFα on apoptosis in malignant and normal human keratinocytes. Methods: Human cutaneous squamous cell carcinoma (SCC) cell line SCC-13 and immortalized human keratinocytes HaCaT as well as primary normal human keratinocytes (PNHK) were stimulated with TNFα and then treated either with TRAIL or 5FU. Cell viability and cell proliferation, DNA fragmentation, apoptosis, and cytotoxicity were determined by WST-1 proliferation assay, ELISA, flow cytometry, and colorimetric analysis of lactate dehydrogenase, respectively. In addition, Western blotting was performed for analysis of caspase-3. Results: TNFα affected viability of SCC-13 and HaCaT cells in combination with 5FU or TRAIL. In contrast, TNFα did not influence cell viability of PNHK. It enhanced the apoptotic effects of both extrinsic and intrinsic stimuli in SCC-13 and HaCaT. In clear contrast, TNFα protected PNHK against TRAIL- and 5FU-induced apoptosis. The effects were dose-dependent and TNFα-specific; furthermore, the apoptosis pathway was caspase-dependent. Conclusions: In summary, opposing effects of TNFα in malignant versus normal human keratinocytes were observed with possibly relevant clinical implications, when patients are treated with TNFα inhibitors.

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