Low‐dose radiotherapy (LD‐RT) and the modulation of iNOS expression in adjuvant‐induced arthritis in rats

Hildebrandt, Guido; Radlingmayr, A.; Rosenthal, Susan; Rothe, R.; Jahns, J; Hindemith, Marion; Rödel, Franz; Kamprad, F

doi:10.1080/09553000310001636639

Cited by 73 publications

(51 citation statements)

References 19 publications

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“…Many of these effects persisted at 9 months. Our results are in accordance with some reports showing the anti-inflammatory effect of low-dose irradiation [51,61] and of low dose radiotherapy (<1Gy or fractionated) [62][63][64].…”

Section: Discussionsupporting

confidence: 83%

Chronic internal exposure to low dose 137CS induces positive impact on the stability of atherosclerotic plaques by reducing inflammation in APOE-/- MICE

et al. 2015

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After Chernobyl and Fukushima Daï Chi, two major nuclear accidents, large amounts of radionuclides were released in the environment, mostly caesium 137 ( 137 Cs). Populations living in contaminated territories are chronically exposed to radionuclides by ingestion of contaminated food. However, questions still remain regarding the effects of low dose ionizing radiation exposure on the development and progression of cardiovascular diseases. We therefore investigated the effects of a chronic internal exposure to 137 Cs on atherosclerosis in predisposed ApoE -/-mice. Mice were exposed daily to 0, 4, 20 or 100 kBq/l 137 Cs in drinking water, corresponding to range of concentrations found in contaminated territories, for 6 or 9 months. We evaluated plaque size and phenotype, inflammatory profile, and oxidative stress status in different experimental groups. Results did not show any differences in atherosclerosis progression between mice exposed to 137 Cs and unexposed controls. However, 137 Cs exposed mice developed more stable plaques with decreased macrophage content, associated with reduced aortic expression of pro-inflammatory factors (CRP, TNFα, MCP-1, IFNγ) and adhesion molecules (ICAM-1, VCAM-1 and E-selectin). Lesions of mice exposed to 137 Cs were also characterized by enhanced collagen and smooth muscle cell content, concurrent with reduced matrix metalloproteinase MMP8 and MMP13 expression. These results suggest that low dose chronic exposure of 137 Cs in ApoE -/-mice enhances atherosclerotic lesion stability by inhibiting pro-inflammatory cytokine and MMP production, resulting in collagen-rich plaques with greater smooth muscle cell and less macrophage content.

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Section: Discussionsupporting

confidence: 83%

Chronic internal exposure to low dose 137CS induces positive impact on the stability of atherosclerotic plaques by reducing inflammation in APOE-/- MICE

et al. 2015

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“…In subsequent decades, these characteristics were confirmed in a variety of inducible inflammatory models in rabbits, rats, and, more recently, in human tumor necrosis factor α(TNF-α) transgenic mice [19]. These models convincingly indicate that low-dose irradiation inhibits proliferation of synovial cells and synthesis of synovial fluid, reduces the destruction of cartilage and bone, hampers expression of iNOS and IL-1, and increases secretion of the anti-inflammatory cytokine TGF-β1 concomitant with an increased expression of heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1; [3,8,18,26,54,59]). Notably, very recent in vitro data confirmed an inhibition of IL-1β-induced catenin signaling by LD-RT, with subsequent suppression of the sex-determining region Y-box 9 (Sox-9) transcription factor and NF-κB pathways in articular chondrocytes, which may well contribute to the palliation of pathophysiological processes in cartilage disorders [30].…”

Section: Preclinical Modelsmentioning

confidence: 99%

DEGRO practical guidelines for radiotherapy of non-malignant disorders

Reichl

Block²,

Schäfer

et al. 2015

Strahlenther Onkol

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“…Namely, these were single doses of 0.3-1.0 Gy in 4-5 fractions for acute and 1-3 fractions for chronic diseases per week to total doses of 3-5 Gy and 12 Gy, respectively (Seegenschmiedt et al, 1997). In animal studies, there are reports that indicated the anti-inflammatory effect and the reduction of clinical symptoms if the local irradiations were given with daily fractionated doses of 5 x0.5 Gy, total dose was 2.5 Gy (Hildebrandt et al, 2000(Hildebrandt et al, , 2003. In Nakatsukasa et al's reports (2008Nakatsukasa et al's reports ( , 2010, the whole body irradiation was conducted, therefore somewhat higher doses than that of local irradiation might be applied.…”

Section: Foxp3mentioning

confidence: 99%

“…Therefore the authors of our referenced papers might take clinically low dose irradiation into consideration because they finally aimed to develop new therapies for above diseases. Moreover, there are some reports that investigated the mechanism of LD-RT using the animal models (Hildebrandt et al 2000(Hildebrandt et al , 2003Rödel et al 2007). 0.5 Gy/exposure of γ-or x-ray irradiation was also regarded as low-dose in these animal studies.…”

Section: Introductionmentioning

confidence: 99%

Effects of Low-Dose-Gamma Rays on the Immune System of Different Animal Models of Disease

Shimura

Kojima

2014

Dose-Response

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ᮀ We reviewed the beneficial or harmful effects of low-dose ionizing radiation on several diseases based on a search of the literature. The attenuation of autoimmune manifestations in animal disease models irradiated with low-dose γ-rays was previously reported by several research groups, whereas the exacerbation of allergic manifestations was described by others. Based on a detailed examination of the literature, we divided animal disease models into two groups: one group consisting of collagen-induced arthritis (CIA), experimental encephalomyelitis (EAE), and systemic lupus erythematosus, the pathologies of which were attenuated by low-dose irradiation, and another group consisting of atopic dermatitis, asthma, and Hashimoto's thyroiditis, the pathologies of which were exacerbated by low-dose irradiation. The same biological indicators, such as cytokine levels and Tcell subpopulations, were examined in these studies. Low-dose irradiation reduced interferon (IFN)-gamma (γ) and interleukin (IL)-6 levels and increased IL-5 levels and the percentage of CD4Treg cells in almost all immunological disease cases examined. Variations in these biological indicators were attributed to the attenuation or exacerbation of the disease's manifestation. We concluded that autoimmune diseases caused by autoantibodies were attenuated by low-dose irradiation, whereas diseases caused by antibodies against external antigens, such as atopic dermatitis, were exacerbated.

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Low‐dose radiotherapy (LD‐RT) and the modulation of iNOS expression in adjuvant‐induced arthritis in rats

Cited by 73 publications

References 19 publications

Chronic internal exposure to low dose 137CS induces positive impact on the stability of atherosclerotic plaques by reducing inflammation in APOE-/- MICE

Chronic internal exposure to low dose 137CS induces positive impact on the stability of atherosclerotic plaques by reducing inflammation in APOE-/- MICE

DEGRO practical guidelines for radiotherapy of non-malignant disorders

Effects of Low-Dose-Gamma Rays on the Immune System of Different Animal Models of Disease

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