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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：

PURPOSE: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). MATERIALS AND 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.

journal_name

Int J Radiat Biol

journal_title

International journal of radiation biology

authors

Lödermann B,Wunderlich R,Frey S,Schorn C,Stangl S,Rödel F,Keilholz L,Fietkau R,Gaipl US,Frey B

doi

10.3109/09553002.2012.689464

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

727-34

issue

eissn

0955-3002

issn

1362-3095

journal_volume

pub_type

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Low dose ionising radiation leads to a NF-κB dependent decreased secretion of active IL-1β by activated macrophages with a discontinuous dose-dependency.