Mercury modulates interplay between IL-1β, TNF-α, and gap junctional intercellular communication in keratinocytes: mitigation by lycopene
Open accessAbstract
Gap junctional intercellular communication (GJIC) is used to control cell proliferation. It is not surprising then that a lack of GJIC (i.e., during loss of contact inhibition among adjacent cells) is associated with cancer promotion/progression. There also seems to be a link between ineffective GJIC and increases in inflammatory events. Interestingly, many cytokines released during an inflammatory response also have critical roles in cancer cell survival. Specifically, TNFalpha and IL-1beta are important for initiating/augmenting CD8(+)- and NK-cell mediated killing; however, in what appears counterintuitive, each--at times--can act to protect cancer cells against apoptosis, a major mechanism for cell killing from within. It is thus plausible to assume that certain toxicants might act as cancer promoters in manners distinct from/augmentive of direct effects on DNA, i.e., by concurrently altering GJIC and cytokine formation in host or microenvironment of a cancer cell. Our research has evaluated effects of many toxicants upon keratinocytes; in particular, we have examined effects of mercury on GJIC and on TNFalpha and IL-1beta levels in (and secretion by) these cells. In the studies here, a tomato preparation (i.e., an oleoresin) bearing the antioxidant carotenoid lycopene was examined for its effects on GJIC and cytokine formation by keratinocytes in general, and its potential ability to mitigate/reverse the toxic effects of mercury in the cells in particular. It was shown that a 4-hr treatment with the oleoresin (containing 56, 6 nM lycopene) re-established GJIC among--and increased the formation of IL-1beta and TNFalpha that had been significantly reduced within--keratinocytes that had been pre-treated for 24 hr with 10 nM HgCl(2). These results show that effects of mercury likely depend on some level of oxidative stress and that its potential effects on keratinocyte GJIC and cytokine concentrations could, in an exposed host, be mitigated/reversed by increased dietary intake of carotenoids like lycopene.
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Lycopene has been shown to inhibit proliferation of several types of cancer cells through different mechanisms in in vitro systems.
“In fact, lycopene has been shown to inhibit proliferation of several types of cancer cells through different mechanisms in in vitro systems [10, 11].”
From The Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes (2016) · cites this paper as [11]
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The Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes
Ascenso, A., Pedrosa, T., Pinho, S., Pinho, F., Oliveira, J. M. P. F. D., Cabral Marques, H., Oliveira, H., Simões, S., & Santos, C. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/8214631 · Cited by 57 · see citing works
- Authors
- Zefferino, R., Leone, A., Piccaluga, S., Cincione, R., & Ambrosi, L.
- Affiliations
- University of Foggia (IT)
- National Research Council (IT)
- Fondazione Salvatore Maugeri (IT)
- Corresponding author
- Zefferino, Roberto
- Venue
- Journal of Immunotoxicology
- Publisher
- Informa UK Limited
- Published
- 2008-01
- Volume
- 5
- Issue
- 4
- Pages
- 353-360
- ISSN
- 1547-6901 (ISSN-L)
- 1547-691X
- OpenAlex
- W2139507872
- Cited by
- 22
- References
- 66
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 2 · 2019: 2 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Immunotoxicology (publishedVersion)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Mercury impact and mitigation studies
- Keywords
- mercury toxicity, gap junctional intercellular communication, keratinocytes, IL-1β, TNF-α, lycopene, carotenoids, oxidative stress, cytokine production, contact inhibition, tumor promotion, dietary antioxidants
- MeSH terms
- Lycopene, Carotenoids, Cell Communication, Cells, Cultured, Humans, Lipopolysaccharides, Mercuric Chloride, Mercury, Plant Extracts, Tumor Necrosis Factor-alpha, Keratinocytes, Anticarcinogenic Agents, Gap Junctions, Solanum lycopersicum, Interleukin-1beta
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