title: NF-kappa B, cytokines, proteasomes, and low-dose radiation exposure.
abstract: Ionizing radiation shares with proinflammatory cytokines a pathway that involves reactive oxygen species and activation of the redox-sensitive nuclear transcription factor NF-kappa B, which leads to expression of inflammatory and cell survival programs. NF-kappa B activation normally requires phosphorylation of its inhibitor I kappa B and the inhibitor's subsequent degradation by the proteasome. Nonlinear dose-response curves have been reported for both radiation-induced cytokines and NF-kappa B and I kappa B expression with maximum exposures of less than 2 Gy and greater than 4 Gy, respectively. Radiation-inhibited proteasomes function over a wide dose range, suggesting that the proteasome is a redox-sensitive target for radiation that may function along with transcription to cause nonlinear dose-response relationships for early expression of many molecules, including NF-kappa B and cytokines. These pathways are relevant to low-dose radiation effects, adaptive responses, and carcinogenesis.
authors.affiliation: Roy E. Coats Laboratories, Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA 90064, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: McBride
authors.forename: Frank
authors.initials: F
authors.lastname: Pajonk
authors.forename: Chi-Shuin
authors.initials: CS
authors.lastname: Chiang
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Sun
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases; D016207:Cytokines; D051379:Mice; D009097:Multienzyme Complexes; D016328:NF-kappa B; D046988:Proteasome Endopeptidase Complex; D011829:Radiation Dosage
chemical_list: D016207:Cytokines; D009097:Multienzyme Complexes; D016328:NF-kappa B; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex