Low doses of ionizing radiation induce immune-stimulatory responses in isolated human primary monocytes

El‐Saghire, Houssein; Michaux, Arlette; Thierens, Hubert; Baatout, Sarah

doi:10.3892/ijmm.2013.1514

Cited by 56 publications

(43 citation statements)

References 45 publications

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“…12). Other investigators have reported similar observations in human monocytes treated with purified HMGB1 (32,68). Monocytes and macrophages are the key players in orchestrating the immune response to infection and injury.…”

Section: Fig 11supporting

confidence: 62%

Respiratory Syncytial Virus Infection Triggers Epithelial HMGB1 Release as a Damage-Associated Molecular Pattern Promoting a Monocytic Inflammatory Response

Hosakote

Brasier

Casola

et al. 2016

J Virol

105

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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infant and elderly populations worldwide. Currently, there is no efficacious vaccine or therapy available for RSV infection. The molecular mechanisms underlying RSV-induced acute airway disease and associated long-term consequences remain largely unknown; however, experimental evidence suggests that the lung inflammatory response plays a fundamental role in the outcome of RSV infection. High-mobility group box 1 (HMGB1) is a nuclear protein that triggers inflammation when released from activated immune or necrotic cells and drives the pathogenesis of various infectious agents. Although HMGB1 has been implicated in many inflammatory diseases, its role in RSV-induced airway inflammation has not been investigated. This study investigates the molecular mechanism of action of extracellularly released HMGB1 in airway epithelial cells (A549 and small airway epithelial cells) to establish its role in RSV infection. Immunofluorescence microscopy and Western blotting results showed that RSV infection of human airway epithelial cells induced a significant release of HMGB1 as a result of translocation of HMGB1 from the cell nuclei to the cytoplasm and subsequent release into the extracellular space. Treating RSV-infected A549 cells with antioxidants significantly inhibited RSV-induced HMGB1 extracellular release. Studies using recombinant HMGB1 triggered immune responses by activating primary human monocytes. Finally, HMGB1 released by airway epithelial cells due to RSV infection appears to function as a paracrine factor priming epithelial cells and monocytes to inflammatory stimuli in the airways. IMPORTANCERSV is a major cause of serious lower respiratory tract infections in young children and causes severe respiratory morbidity and mortality in the elderly. In addition, to date there is no effective treatment or vaccine available for RSV infection. The mechanisms responsible for RSV-induced acute airway disease and associated long-term consequences remain largely unknown. The oxidative stress response in the airways plays a major role in the pathogenesis of RSV. HMGB1 is a ubiquitous redox-sensitive multifunctional protein that serves as both a DNA regulatory protein and an extracellular cytokine signaling molecule that promotes airway inflammation as a damage-associated molecular pattern. This study investigated the mechanism of action of HMGB1 in RSV infection with the aim of identifying new inflammatory pathways at the molecular level that may be amenable to therapeutic interventions. R espiratory syncytial virus (RSV) is a ubiquitous, negativesense, enveloped, single-stranded RNA virus that frequently causes upper and lower respiratory tract infections in infants, young children, the elderly, and immunocompromised individuals. Epidemiological evidence indicates that severe pulmonary disease caused by RSV infection in infancy is associated with recurrent wheezing and the development of asthma later in childhood. No ...

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Section: Fig 11supporting

confidence: 62%

Respiratory Syncytial Virus Infection Triggers Epithelial HMGB1 Release as a Damage-Associated Molecular Pattern Promoting a Monocytic Inflammatory Response

Hosakote

Brasier

Casola

et al. 2016

J Virol

105

View full text Add to dashboard Cite

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“…The authors of previous research have reported that cardiovascular morbidity and mortality may occur decades after ionizing radiation exposure (Yan et al, 2014). The health risks arising from exposure to low doses of ionizing radiation should be re-evaluated (El-Saghire et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Sperm quality and DNA damage in men from Jilin Province, China, who are occupationally exposed to ionizing radiation

Zhou¹,

Hao²,

Guo³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Long-term radiation exposure affects human health. Ionizing radiation has long been known to raise the risk of cancer. In addition to high doses of radiation, low-dose ionizing radiation might increase the risk of cardiovascular disease, lens opacity, and some other non-cancerous diseases. Low-and high-dose exposures to ionizing radiation elicit different signaling events at the molecular level, and may involve different response mechanisms. The health risks arising from exposure to low doses of ionizing radiation should be re-evaluated. Health workers exposed to ionizing radiation experience low-dose radiation and have an increased risk of hematological malignancies. Reproductive function is sensitive to changes in the physical environment, including ionizing radiation. However, data is scarce regarding the association between occupational radiation exposure and risk to human fertility. Sperm DNA integrity is a functional parameter of male fertility evaluation. Hence, we aimed to report sperm quality and DNA damage in men from Jilin Province, China, who were occupationally exposed to ionizing radiation. Sperm motility and normal morphology were significantly lower in the exposed compared with the non-exposed men. There was no statistically significant difference in sperm concentration between exposed and non-exposed men. The sperm DNA fragmentation index was significantly higher in the exposed than the non-exposed men. Chronic long-term exposure to low doses of ionizing radiation could affect sperm motility, normal morphology, and the sperm DNA fragmentation index in the Chinese population. Sperm quality and DNA integrity are functional parameters that could be used to evaluate occupational exposure to ionizing radiation.

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“…The health risks arising from exposure to low doses of IR have been identified in previous studies (Kamiya et al, 2015), and should be re-evaluated (El-Saghire et al, 2013). The incidences of cataracts are closely associated with IR exposure (Shore et al, 2010;Kleiman, 2012).…”

Section: Discussionmentioning

confidence: 92%

Cytogenetic evaluation of cataract patients occupationally exposed to ionizing radiation in northeast China

Yao

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Long-term radiation exposure is hazardous to health; late-onset effects of exposure to ionizing radiation (IR) pose risks to the lens, and are associated with other non-cancerous diseases. Individuals occupationally exposed to low-dose IR are prone to developing eye cataracts. Cytogenetic evaluations suggest that IR is associated with chromosomal aberrations in occupationally exposed individuals. However, data regarding the association between chromosomal aberrations in cataract patients and occupational exposure to IR is scarce. Therefore, we aimed to report the characteristics of chromosomal aberrations in cataract patients from a Chinese population, occupationally exposed to IR. We found that the average age and frequency of numerical chromosomal aberrations were significantly lower in the exposed patients as compared with that in the non-exposed patients. In addition, the frequencies of dicentric and acentric chromosomes were significantly higher in the exposed patients as compared with those in the non-exposed patients. Therefore, chronic occupational exposure to IR affects cataract development in the Chinese population. The age of cataract patients exposed to IR was significantly lower than the age of cataract onset in normal individuals. Based on this study, we suggest that there is an urgent need for improved radiation safety and eye protection in individuals exposed to IR in the work place.

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Low doses of ionizing radiation induce immune-stimulatory responses in isolated human primary monocytes

Cited by 56 publications

References 45 publications

Respiratory Syncytial Virus Infection Triggers Epithelial HMGB1 Release as a Damage-Associated Molecular Pattern Promoting a Monocytic Inflammatory Response

Respiratory Syncytial Virus Infection Triggers Epithelial HMGB1 Release as a Damage-Associated Molecular Pattern Promoting a Monocytic Inflammatory Response

Sperm quality and DNA damage in men from Jilin Province, China, who are occupationally exposed to ionizing radiation

Cytogenetic evaluation of cataract patients occupationally exposed to ionizing radiation in northeast China

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