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Cited by 19Genomics, phytochemicals, and oxidative stressAntioxidant Activity and Oxidative StressNF-κB Signaling Pathways

Modulation of NF-κB and Nrf2 control of inflammatory responses in FHs 74 Int cell line is tocopherol isoform-specific

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Elisia, Ingrid, Kitts, David D.·2013·American Journal of Physiology-Gastrointestinal and Liver Physiology
DOI 10.1152/ajpgi.00269.2013PMC PMC3882439
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Abstract

The present study investigates the relative ability of α-, γ-, and δ-tocopherol (Toc) to modulate cell signaling events that are associated with inflammatory responses in fetal-derived intestinal (FHs 74 Int) cells. Secretion of the proinflammatory cytokine IL-8 in FHs 74 Int cells was stimulated in the following order: α-Toc < γ-Toc < δ-Toc. A similar proinflammatory response was observed when inflammation was induced in FHs 74 Int cells. Modulation of IL-8 expression by Toc corresponded to an isoform-specific modulation of NF-κB and nuclear factor-erythroid 2-related factor 2 (Nrf2) cell signaling pathways involved in expression of proinflammatory cytokines and antioxidant enzymes, respectively. δ-Toc and, to a lesser extent, γ-Toc activated NF-κB and Nrf2 signaling, as indicated by the greater nuclear translocation of transcription factors. Activation of NF-κB signaling by γ- and δ-Toc was accompanied by upregulation of NF-κB target genes, such as IL-8 and prostaglandin-endoperoxide synthase 2, with and without a prior IFNγ-PMA challenge. Nevertheless, γ- and δ-Toc, particularly δ-Toc, concurrently downregulated glutamate-cysteine ligase, a Nrf2 target gene that encodes for glutathione biosynthesis. This observation was substantiated by confirmation that γ- and δ-Toc were effective at decreasing glutamate-cysteine ligase protein expression and cellular glutathione content. Downregulation of glutathione content in fetal intestinal cells corresponded to induction of apoptosis-mediated cytotoxicity. In conclusion, γ- and δ-Toc are biologically active isoforms of vitamin E and show superior bioactivity to α-Toc in modulating cell signaling events that contribute to a proinflammatory response in fetal-derived intestinal cells.

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  • Normal diploid cell lines CCC-HIE-2, FHC and FSH-74int established by the Chinese Academy of Medical Sciences had been shown to be actually derived from HeLa cells.

    “Normal diploid cell lines, namely CCC-HIE-2, FHC and FSH-74int, established by the Chinese Academy of Medical Sciences [32, 33], respectively, had been shown to be actually derived from HeLa cells.”

    From Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines (2017) · cites this paper as [33]

    The Materials and Methods (Cell culture; page unavailable) describes FHs 74 Int as a primary cell line derived from a human fetal small intestine, contrary to the claim that it was derived from HeLa cells. Our copy does not address HeLa derivation of CCC-HIE-2 or FHC. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Elisia, I., & Kitts, D. D.
Affiliations
University of British Columbia (CA)
Corresponding author
Kitts, David D.
ORCID
Venue
American Journal of Physiology-Gastrointestinal and Liver Physiology
Publisher
American Physiological Society
Published
2013-12-15
Volume
305
Issue
12
Pages
G940-G949
ISSN
  • 0193-1857 (ISSN-L)
  • 1522-1547
DOI
10.1152/ajpgi.00269.2013
PMC
PMC3882439
OpenAlex
W2164425787
Cited by
19
References
3
Citations by year
2026: 1 · 2024: 2 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 4
FWCI
0.90
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
vitamin E, NF-κB signaling, Nrf2 signaling, interleukin-8, delta-tocopherol, gamma-tocopherol, alpha-tocopherol, glutathione, gamma-glutamylcysteine synthetase, cyclooxygenase-2, apoptosis, inflammation, antioxidant enzymes
MeSH terms
Antioxidants, Cells, Cultured, Humans, Inflammation, Intestine, Small, Signal Transduction, NF-kappa B, Gene Expression Profiling, Tocopherols, Fetal Research, NF-E2-Related Factor 2

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