The Nuclear Factor κB pathway: A link to the immune system in the radiation response
- PMID: 25688671
- DOI: 10.1016/j.canlet.2015.02.019
The Nuclear Factor κB pathway: A link to the immune system in the radiation response
Abstract
Exposure to ionizing radiation modulates immune responses in a complex dose-dependent pattern, with possible anti-inflammatory effects in the low dose range, expression of pro-inflammatory cytokines at moderate doses and immunosuppression after exposure to higher doses due to precursor cell death together with concomitant exacerbated innate immune responses. A central regulator in the immune system is the transcription factor Nuclear Factor κB (NF-κB). NF-κB is involved in the regulation of cellular survival, immune responses and inflammation, resulting in eminent importance in cancerogenesis. After exposure to ionizing radiation, NF-κB activation is initially triggered by ATM which is activated by DNA double strand breaks. Together with the NF-κB essential modulator (NEMO), it serves as a nucleoplasmic shuttle. The pathway converges with the classical NF-κB pathway at IκB kinase (IKK) complex activation. Resulting cytokine expression can activate NF-κB in a positive feed forward loop. Danger signals released from dying cells can activate NF-κB via Toll-like receptors (TLRs). The resulting immune activation can be beneficial or detrimental. In the low dose range, pro- and anticancerogenic effects are possible. In the radiotherapy-relevant dose range, tolerogenic immune responses should be avoided, and an anti-tumor immune response might be supported by TLR agonists activating NF-κB.
Keywords: Bystander effect; Cellular radiation response; Chemokines; Immune system; Linear energy transfer; Nuclear Factor κB.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Similar articles
-
Low doses of ionizing radiation induce immune-stimulatory responses in isolated human primary monocytes.Int J Mol Med. 2013 Dec;32(6):1407-14. doi: 10.3892/ijmm.2013.1514. Epub 2013 Sep 30. Int J Mol Med. 2013. PMID: 24085242
-
Signaling to NF-kappaB by Toll-like receptors.Trends Mol Med. 2007 Nov;13(11):460-9. doi: 10.1016/j.molmed.2007.09.002. Epub 2007 Oct 29. Trends Mol Med. 2007. PMID: 18029230 Review.
-
Epithelial NEMO links innate immunity to chronic intestinal inflammation.Nature. 2007 Mar 29;446(7135):557-61. doi: 10.1038/nature05698. Epub 2007 Mar 14. Nature. 2007. PMID: 17361131
-
Regulation and function of IKK and IKK-related kinases.Sci STKE. 2006 Oct 17;2006(357):re13. doi: 10.1126/stke.3572006re13. Sci STKE. 2006. PMID: 17047224 Review.
-
Viral strategies in modulation of NF-kappaB activity.Arch Immunol Ther Exp (Warsz). 2003;51(6):367-75. Arch Immunol Ther Exp (Warsz). 2003. PMID: 14692658 Review.
Cited by
-
NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia.Int J Mol Sci. 2024 Apr 19;25(8):4495. doi: 10.3390/ijms25084495. Int J Mol Sci. 2024. PMID: 38674080 Free PMC article.
-
A peptide encoded by the circular form of the SHPRH gene induces apoptosis in neuroblastoma cells.PeerJ. 2024 Jan 23;12:e16806. doi: 10.7717/peerj.16806. eCollection 2024. PeerJ. 2024. PMID: 38282862 Free PMC article.
-
Nanosponge hydrogel of octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate of Alcaligenes faecalis.Appl Microbiol Biotechnol. 2024 Dec;108(1):100. doi: 10.1007/s00253-023-12819-3. Epub 2024 Jan 12. Appl Microbiol Biotechnol. 2024. PMID: 38217256 Free PMC article.
-
Lost in Space? Unmasking the T Cell Reaction to Simulated Space Stressors.Int J Mol Sci. 2023 Nov 29;24(23):16943. doi: 10.3390/ijms242316943. Int J Mol Sci. 2023. PMID: 38069265 Free PMC article.
-
Paneth cell dysfunction in radiation injury and radio-mitigation by human α-defensin 5.Front Immunol. 2023 Aug 10;14:1174140. doi: 10.3389/fimmu.2023.1174140. eCollection 2023. Front Immunol. 2023. PMID: 37638013 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous