Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899413 | Cancer Letters | 2015 | 15 Pages |
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
NF-κBPI3KMMPDSBLPSPARP-1DAMPsNREDDRMEFPAMPsiNOSHUVECPGE2MCP-1RNSNEMOIκBTLRIAPIKKICAM1PRRARDBtg2B-cell translocation gene 2RHDCXCLTABVCAM-1TregsTNFRSV40TAK1CCL3SASPT helperTRAFXIAPChemokine (C-C motif) ligand 3PIDDNIKLRRGadd45bRIP1MD-2DNA-PKBIRCβ-TrCPUBC13Phosphatidyl-inositol 3-kinasePIASySUMO-1NF-κB-inducing kinaseX-linked IAPEMSAnatural killerDUSPIκB kinaseMAPKMAPK kinase kinaseROSElectrophoretic mobility shift assayAnkyrin repeat domainLETdamage-associated molecular patternspathogen-associated molecular patternsLinear Energy Transferepithelial mesenchymal transitionEBVinterferonIFNinterleukinChoTADBystander effectChinese Hamster Ovarytumor necrosis factor αleucine-rich repeatEMTToll-like receptorhigh-mobility group box 1dual specificity phosphataseATMTranscriptional activation domainRel homology domainImmune systemhoursHuman umbilical vein endothelial cellsRegulatory T cellsinducible nitric oxide synthasedouble strand breakVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)TNF-αnuclear factor κBSenescence-associated secretory phenotypemurine embryonic fibroblastslipopolysaccharidechemokine (C-X-C motif) ligand matrix metalloproteinaseMHCmajor histocompatibility complexNF-κB essential modulatorElksinhibitor of NF-κBinhibitor of apoptosisintercellular adhesion moleculevascular cell adhesion molecule-1DNA-dependent protein kinaseDNA damage responseEpstein–Barr virusSimian virus 40Monocyte chemotactic protein-1mitogen-activated protein kinasereceptor interacting protein 1Prostaglandin E2Chemokineshuman embryonic kidneyreactive nitrogen speciesReactive oxygen speciesTNF receptorpattern recognition receptors
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cancer Research
Authors
Christine E. Hellweg,