Cited by 2,793NF-κB Signaling PathwaysCytokine Signaling Pathways and InteractionsCell death mechanisms and regulation

Signalling pathways of the TNF superfamily: a double-edged sword

Aggarwal, Bharat B.·2003·Nature Reviews Immunology

Abstract

Two different tumour-necrosis factors (TNFs), first isolated in 1984, were found to be cytotoxic to tumour cells and to induce tumour regression in mice. Research during the past two decades has shown the existence of a superfamily of TNF proteins consisting of 19 members that signal through 29 receptors. These ligands, while regulating normal functions such as immune responses, haematopoiesis and morphogenesis, have also been implicated in tumorigenesis, transplant rejection, septic shock, viral replication, bone resorption, rheumatoid arthritis and diabetes; so indicating their role as 'double-edged swords'. These cytokines either induce cellular proliferation, survival, differentiation or apoptosis. Blockers of TNF have been approved for human use in treating TNF-linked autoimmune diseases in the United States and other countries.

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Crossref · 10.1038/nri1184

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124 of 124 references verified0 citation errors · 0 not checkable

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  • TNF-α is a pro-inflammatory cytokine and a potent activator of NF-κB, which induces many pro-mitogenic, pro-inflammatory, and anti-apoptotic proteins, promoting cell proliferation and survival.

    “TNF-α is a pro-inflammatory cytokine and a potent activator of the transcription factor NF-κB, which induces the expression of a multitude of pro-mitogenic, pro-inflammatory, and anti-apoptotic proteins, thus promoting cell proliferation and survival [102].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [102]

  • TNF-α is also a powerful apoptotic inducer in vitro when NF-κB signaling is blocked, typically by cycloheximide.

    “However, TNF-α is also a powerful apoptotic inducer in vitro when NF-κB signaling is blocked, typically by the addition of cycloheximide.”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [102]

  • TNFα acts on its receptors to promote either cell survival or cell death.

    “Tumor necrosis factor alpha (TNFα) is a pleiotropic cytokine that acts on its receptors (TNFRs) to promote either cell survival or cell death 54.”

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Authors
Aggarwal, B. B.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Aggarwal, Bharat B.
Venue
Nature Reviews Immunology
Published
2003-09
Volume
3
Issue
9
Pages
745-756
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
OpenAlex
W2095013915
Cited by
2,793
References
124
Citations by year
2026: 74 · 2025: 107 · 2024: 82 · 2023: 121 · 2022: 125 · 2021: 114 · 2020: 132 · 2019: 113 · 2018: 114 · 2017: 130 · 2016: 108 · 2015: 142 · 2014: 128 · 2013: 116 · 2012: 159
FWCI
9.77
Type
journal article
Language
en
Open access
closed
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
TNF superfamily, TNF-α, TNF receptor, signaling pathways, carcinogenesis, graft rejection, septic shock, viral replication, bone resorption, rheumatoid arthritis, diabetes mellitus, apoptosis, TNF-alpha inhibitors, autoimmune disease, cytokines
MeSH terms
Animals, Autoimmune Diseases, Carrier Proteins, Humans, Ligands, Lymphotoxin-alpha, Membrane Proteins, Tumor Necrosis Factor-alpha, Signal Transduction, NF-kappa B, Receptors, Tumor Necrosis Factor, Mice

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