TNF-α promotes cell survival through stimulation of K+ channel and NFκB activity in corneal epithelial cells
Open accessAbstract
Tumor necrosis factor (TNF-alpha) in various cell types induces either cell death or mitogenesis through different signaling pathways. In the present study, we determined in human corneal epithelial cells how TNF-alpha also promotes cell survival. Human corneal epithelial (HCE) cells were cultured in DMEM/F-12 medium containing 10% FBS. TNF-alpha stimulation induced activation of a voltage-gated K+ channel detected by measuring single channel activity using patch clamp techniques. The effect of TNF-alpha on downstream events included NFkappaB nuclear translocation and increases in DNA binding activities, but did not elicit ERK, JNK, or p38 limb signaling activation. TNF-alpha induced increases in p21 expression resulting in partial cell cycle attenuation in the G1 phase. Cell cycle progression was also mapped by flow cytometer analysis. Blockade of TNF-alpha-induced K+ channel activity effectively prevented NFkappaB nuclear translocation and binding to DNA, diminishing the cell-survival protective effect of TNF-alpha. In conclusion, TNF-alpha promotes survival of HCE cells through sequential stimulation of K+ channel and NFkappaB activities. This response to TNF-alpha is dependent on stimulating K+ channel activity because following suppression of K+ channel activity TNF-alpha failed to activate NFkappaB nuclear translocation and binding to nuclear DNA.
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TNF-α activates NFκB in many different cell types.
“Several other studies document that TNF-α activates NFκB in many different cell types and additionally corneal epithelial wound healing may be modulated by a mechanism involving TNF-α/NFκB regulation of cell-cycle, and therefore proliferation and migration (Wang et al., 2005).”
From Thymosin beta 4 suppression of corneal NFκB: A potential anti-inflammatory pathway (2007) · cites this paper as Wang et al., 2005
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- Authors
- Wang, L., Reinach, P., & Lu, L.
- Affiliations
- University of California, Los Angeles (US)
- SUNY College of Optometry (US)
- Corresponding author
- Lu, Luo
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 311
- Issue
- 1
- Pages
- 39-48
- ISSN
- 0014-4827 (ISSN-L)
- PMC
- PMC1920499
- OpenAlex
- W1989102627
- Cited by
- 27
- References
- 50
- Citations by year
- 2024: 3 · 2023: 3 · 2021: 1 · 2020: 1 · 2016: 2 · 2014: 1 · 2012: 1
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R01EY015281, EY 12953, EY04795, R01EY012953, EY15282, R01EY004795, R56EY004795)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- TNF-α, corneal epithelial cells, cell survival, voltage-gated potassium channels, NF-κB nuclear translocation, p21, G1 cell cycle arrest, corneal wound healing, TNF signaling
- MeSH terms
- Cell Nucleus, Cell Survival, Cells, Cultured, DNA, Flow Cytometry, Humans, Tumor Necrosis Factor-alpha, Potassium Channels, G1 Phase, NF-kappa B, Epithelium, Corneal, Mitogen-Activated Protein Kinases, Protein Transport, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases
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