Low dose ionising radiation leads to a NF-κB dependent decreased secretion of active IL-1β by activated macrophages with a discontinuous dose-dependency
| Autor: | Roland Wunderlich, Ludwig Keilholz, Barbara Lödermann, Silke Frey, Franz Rödel, Christine Schorn, Rainer Fietkau, Sonja Stangl, Benjamin Frey, Udo S. Gaipl |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharide
p38 mitogen-activated protein kinases Interleukin-1beta Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Western blot Cell Line Tumor medicine Humans Radiology Nuclear Medicine and imaging Secretion Protein kinase A Protein kinase B 030304 developmental biology Inflammation 0303 health sciences Radiological and Ultrasound Technology medicine.diagnostic_test Macrophages X-Rays Transcription Factor RelA Dose-Response Relationship Radiation Inflammasome NF-κB Molecular biology 3. Good health chemistry 030220 oncology & carcinogenesis medicine.drug |
| Zdroj: | International Journal of Radiation Biology |
| ISSN: | 1362-3095 0955-3002 |
| DOI: | 10.3109/09553002.2012.689464 |
| Popis: | 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).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.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.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. |
| Databáze: | OpenAIRE |
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