title: Low dose ionising radiation leads to a NF-κB dependent decreased secretion of active IL-1β by activated macrophages with a discontinuous dose-dependency.
abstract: OBJECTIVE
  Therapy with low doses of ionising radiation (X-rays) exerts anti-inflammatory effects. Little is known about whether and how low doses of X-ray treatment modulate the inflammatory phenotype of macrophages, especially the secretion of Interleukin-1beta (IL-1β).
  
  
  METHODS
  Macrophages were differentiated from human THP-1 monocytes, activated with lipopolysaccharide (LPS), treated with distinct low doses of X-rays, and co-activated with monosodium urate crystals (MSU) to induce inflammasome activation. Secretion of IL-1β was analysed by an enzyme-linked immunosorbent assay (ELISA) and Western blot. Furthermore, we analysed the intracellular amounts of the serine/threonine protein kinase B (named: Akt), mitogen-activated protein kinase p38 (p38), the v-rel reticuloendotheliosis viral oncogene homolog A (RelA), and pro- and cleaved IL-1β.
  
  
  RESULTS
  Low dose X-rays led to decreased secretion of active IL-1β in a manner discontinuous with dose which was most pronounced after 0.5 or 0.7 Gy. Passive release of lactate dehydrogenase (LDH) was not influenced by X-rays. The decreased secretion of IL-1β correlated with reduced translocation of RelA, being part of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) complex, into the nucleus. After 0.5 or 0.7 Gy of X-rays, the intracellular protein amounts of up (p38) and downstream molecules (Akt) of NF-κB were reduced in activated macrophages, as were the pro- and cleaved forms of IL-1β.
  
  
  CONCLUSIONS
  Distinct low doses of X-rays induce an anti-inflammatory phenotype of activated macrophages by lowering the amount of secreted IL-1β in a NF-κB dependent manner.
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lödermann
authors.forename: Roland
authors.initials: R
authors.lastname: Wunderlich
authors.forename: Silke
authors.initials: S
authors.lastname: Frey
authors.forename: Christine
authors.initials: C
authors.lastname: Schorn
authors.forename: Sonja
authors.initials: S
authors.lastname: Stangl
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
authors.forename: Ludwig
authors.initials: L
authors.lastname: Keilholz
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.forename: Udo S
authors.initials: US
authors.lastname: Gaipl
authors.forename: Benjamin
authors.initials: B
authors.lastname: Frey
mesh_terms: D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000528:radiation effects*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014965:X-Rays / Q000009:adverse effects
chemical_list: D053583:Interleukin-1beta; D051996:Transcription Factor RelA