{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:12:25Z","timestamp":1791267145595,"version":"4.1.0"},"reference-count":38,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Skin Pharmacol Physiol"],"published-print":{"date-parts":[[2021]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Tumor necrosis factor alpha (TNF\u03b1) 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. &lt;b&gt;&lt;i&gt;Objectives:&lt;\/i&gt;&lt;\/b&gt; To investigate the effects of TNF\u03b1 on apoptosis in malignant and normal human keratinocytes. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; 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 TNF\u03b1 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. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; TNF\u03b1 affected viability of SCC-13 and HaCaT cells in combination with 5FU or TRAIL. In contrast, TNF\u03b1 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, TNF\u03b1 protected PNHK against TRAIL- and 5FU-induced apoptosis. The effects were dose-dependent and TNF\u03b1-specific; furthermore, the apoptosis pathway was caspase-dependent. &lt;b&gt;&lt;i&gt;Conclusions:&lt;\/i&gt;&lt;\/b&gt; In summary, opposing effects of TNF\u03b1 in malignant versus normal human keratinocytes were observed with possibly relevant clinical implications, when patients are treated with TNF\u03b1 inhibitors.<\/jats:p>","DOI":"10.1159\/000513725","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T13:56:13Z","timestamp":1616507773000},"page":"94-102","source":"Crossref","is-referenced-by-count":24,"title":["Ambivalent Effects of Tumor Necrosis Factor Alpha on Apoptosis of Malignant and Normal Human 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