Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma
November
Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma
Joong Sun Kim 0 1 2
Yeonghoon Son 0 1 2
Min Ji Bae 0 1 2
Seung Sook Lee 0 1 2
Sun Hoo Park 0 1 2
Hae June Lee 0 1 2
Soong In Lee 0 1 2
Chang Geun Lee 0 1 2
Sung Dae Kim 0 1 2
Wol Soon Jo 0 1 2
Sung Ho Kim 0 1 2
In Sik Shin 0 1 2
0 1 Research Center, Dongnam institute of Radiological & Medical Sciences (DIRAMS) , Busan , South Korea , 2 Laboratory of Radiation Exposure & Therapeutics , Seoul , South Korea , 3 Division of Radiation effect, Korea institute of Radiological & Medical Sciences (KIRAMS) , Seoul , South Korea , 4 College of Oriental Medicine, Dongshin University , Jeonnam , South Korea , 5 College of Veterinary Medicine, Chonnam National University , Gwangju , South Korea
1 Funding: This work was supported by National R&D Program through the Korea Institute of Radiological and Medical Sciences [50586-2015] and Nuclear R&D Program [50492-2015] of the Ministry of Science, ICT & Future Planning, Korea, and Global ATC program of Ministry of Trade, Industry & Energy , Korea [51316-2014]
2 Editor: Bernhard Ryffel, French National Centre for Scientific Research , FRANCE
Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to lowdose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation.
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OPEN ACCESS
Data Availability Statement: All relevant data are
within the paper and its Supporting Information files.
Competing Interests: The authors have declared
that no competing interests exist.
Introduction
The recent nuclear accident in Japan has increased public concern about the critical effects of
radiation exposure. High-dose and high-dose-rate radiation have been shown to induce
detrimental effects in various organisms, thereby causing cell death [
1
]. In contrast, low-dose
radiation has been reported to exert various beneficial effects [
2, 3
]. These distinct effects are
proportional to the dose and rate of irradiation [
4, 5
]. Low-dose radiation exposure has been a
rising issue in modern society because many people are potentially exposed to it. The safe dose
of this type of radiation has been determined, and the effects of low-dose ( 0.3 Gy) and
lowdose-rate ( 6 mGy/h) radiation have been investigated according to the recommendations of
the United Nations Scientific Committee on the Effects of Atomic Radiation [
6
]. Nonetheless,
the effects of low-dose radiation exposure on the development of diseases have not been
examined. Further investigations on the correlation between low-dose radiation and disease
development are therefore warranted in order to relieve the anxiety of the public.
Asthma is a chronic inflammatory airway disease. Its prevalence has increased in recent
decades, and it generally occurs during childhood or young adulthood [
7
]. It is generally caused
by the inhalation of allergens such as pollens, house dust, inhalants, and air pollutants and is
characterized by eosinophilic airway inflammation, airway hyper-responsiveness, and mucus
hypersecretion [
8
]. Inflammatory cells release various chemical mediators that are closely
associated with asthma development [
9
]. Various studies have demonstrated the relationship
between radiation exposure and the development of asthma [
10–12
], but the results have been
contradictory. While one study reported that radiation exposure induced chronic airway
inflammation, another study demonstrated that the asthmatic response was attenuated by
radiation [
13, 14
]. These conflicting results have been attributed to (...truncated)