title: 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.
authors: German Aerospace Centre (DLR), Institute of Aerospace Medicine, Radiation Biology, Linder Höhe, Köln D-51147, Germany. Electronic address: christine.hellweg@dlr.de.
authors: Christine E
authors: CE
authors: Hellweg
mesh_terms: D000818:Animals; D006801:Humans; D007107:Immune System / Q000378:metabolism / Q000528:radiation effects*; D007113:Immunity, Innate / Q000528:radiation effects*; D016328:NF-kappa B / Q000276:immunology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000276:immunology / Q000528:radiation effects
chemical_list: D016328:NF-kappa B
keywords: Bystander effect; Cellular radiation response; Chemokines; Immune system; Linear energy transfer; Nuclear Factor κB