Sustained elevation of NF‐<i>κ</i>B DNA binding activity in radiation‐induced lung damage in rats

Haase, Michael; Klawitter, Anke; Geyer, Peter; Alheit, H.; Baumann, Michaël; Kriegel, Thomas; Kasper, Michael; Baretton, Gustavo

doi:10.1080/09553000310001632903

Cited by 34 publications

(40 citation statements)

References 57 publications

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“…Nuclear factor kappa B (NF-κB) has been shown to be continuously activated following irradiation and is involved in initiating and sustaining the inflammatory response [97,98]. NF-κB can be activated by a wide variety of stimuli, such as oxidative stress, radiation, LPS exposure, cytokines, bacterial and viral antigens, many of which are involved in the inflammatory response.…”

Section: Lung Inflammation Post Irradiation (Pi) -Nf-κbmentioning

confidence: 99%

Effects of genistein following fractionated lung irradiation in mice

Para¹,

Bezjak²,

Yeung³

et al. 2009

Radiotherapy and Oncology

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Radiation therapy for lung cancer and cancers of the upper thorax is limited by side effects to normal tissue of the lung. An understanding of mechanisms leading to radiation induced lung damage is essential to developing protective agents. In this thesis an anti-oxidant and anti-inflammatory agent Genistein was investigated for its potential to affect DNA damage, tissue inflammation, functional deficits and survival. We hypothesized that chronic oxidative stress and the subsequent inflammatory response play a key role in the development of major lung complications, radiation pneumonitis and fibrosis. If side effects of radiation could be reduced, then larger doses could be delivered to the tumor with a better chance of eradicating the disease.ii Acknowledgements

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Section: Lung Inflammation Post Irradiation (Pi) -Nf-κbmentioning

confidence: 99%

Effects of genistein following fractionated lung irradiation in mice

Para¹,

Bezjak²,

Yeung³

et al. 2009

Radiotherapy and Oncology

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“…At least four animals were studied at each time point, as indicated in previous studies with this system (Haase et al 2000(Haase et al ,2003. Lungs were removed at the indicated time points and either snap-frozen or fixed in Schaffer's solution (64% v/v methanol, 33% v/v of a 40% formaldehyde solution, 3% w/v glucose in PBS) for 24 hr.…”

Section: Animal Modelmentioning

confidence: 99%

“…The right lungs of female Fischer rats were irradiated with 20 Gy of ionizing radiation as previously described (Geyer 1999;Pauluhn et al 2001;Haase et al 2003). At least four animals were studied at each time point, as indicated in previous studies with this system (Haase et al 2000(Haase et al ,2003.…”

Section: Animal Modelmentioning

confidence: 99%

“…Protein extraction and Western blots were done as previously described (Haase et al 2003). The anti-IL-10 antibody was used at a dilution of 1:1000, the peroxidase-labeled secondary antibody at 1:5000.…”

Section: Western Blotsmentioning

confidence: 99%

“…Several proinflammatory cytokines have been described in the process of the disease, including tumor necrosis factor a (TNFa), transforming growth factor b (TGFb), and interleukin-1 (IL-1) (Kovacs 1991;Kovacs and DiPietro 1994). The pro-inflammatory cytokine IL-6, which is induced in pulmonary fibrosis, stimulates proliferation of fibroblasts (Haase et al 2003;Olman et al 2004). One immunomodulatory cytokine that has a potential role in pulmonary fibrosis is IL-10.…”

mentioning

confidence: 99%

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Expression of the Immunomodulator IL-10 in Type I Pneumocytes of the Rat: Alterations of IL-10 Expression in Radiation-induced Lung Damage

Haase

Klawitter

Geyer

et al. 2007

J Histochem Cytochem.

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Fibrosing alveolitis is a disease with inflammatory, proliferative, and fibrotic components. In different models, it has been shown that the cytokine interleukin-10 (IL-10) plays a conflicting role in inflammation-associated fibrotic processes, inasmuch as it is an antiinflammatory cytokine but also a TH2 cytokine with inherent pro-fibrotic effects. IL-10 is produced primarily by inflammatory cells. In this report, we show in a rat model of radiation-induced fibrosing alveolitis that IL-10 is also produced by type I alveolar epithelial cells in both normal and fibrotic lungs. The total amount of IL-10 in the lung is increased after irradiation, but type I pneumoyctes contain less IL-10. The R3/1 permanent type I pneumocyte cell line also contains IL-10, which is reduced after irradiation. Whereas in the normal lung, the entire alveolar surface is covered by IL-10—producing pneumocytes, this continuity is interrupted in fibrotic lungs, because type I pneumocytes lack full differentiation and thus full spreading over the alveolar surface. The exposure of the IL-10—negative epithelial basal membrane may allow for an easier attachment of inflammatory cells such as alveolar macrophages. These cells have the potential to act in a pro-inflammatory way by tumor necrosis factor α and also in a pro-fibrotic way by activating TH2 cytokines.

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Concise Review: Therapeutic Potential of the Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Radiation-Induced Lung Injury: Progress and Hypotheses

Liu

2019

Stem Cells Translational Medicine

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Radiation‐induced lung injury (RILI) is a common complication in radiotherapy of thoracic tumors and limits the therapeutic dose of radiation that can be given to effectively control tumors. RILI develops through a complex pathological process, resulting in induction and activation of various cytokines, infiltration by inflammatory cells, cytokine‐induced activation of fibroblasts, and subsequent tissue remodeling by activated fibroblasts, ultimately leading to impaired lung function and respiratory failure. Increasing evidence shows that mesenchymal stem cells (MSCs) may play a main role in modulating inflammation and immune responses, promoting survival and repair of damaged resident cells and enhancing regeneration of damaged tissue through soluble paracrine factors and therapeutic extracellular vesicles. Therefore, the use of the MSC‐derived secretome and exosomes holds promising potential for RILI therapy. Here, we review recent progress on the potential mechanisms of MSC therapy for RILI, with an emphasis on soluble paracrine factors of MSCs. Hypotheses on how MSC derived exosomes or MSC‐released exosomal miRNAs could attenuate RILI are also proposed. Problems and translational challenges of the therapies based on the MSC‐derived secretome and exosomes are further summarized and underline the need for caution on rapid clinical translation. Stem Cells Translational Medicine 2019;8:344–354

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Sustained elevation of NF‐κB DNA binding activity in radiation‐induced lung damage in rats

Abstract: The DNA binding activity of NF-KappaB is continuously activated after irradiation of the rat lung by loss of nuclear IKappaBAlpha. This might play a role in sustaining chronic inflammation and hyperproliferation of mesenchymal cells after irradiation.

Cited by 34 publications

References 57 publications

Effects of genistein following fractionated lung irradiation in mice

Effects of genistein following fractionated lung irradiation in mice

Expression of the Immunomodulator IL-10 in Type I Pneumocytes of the Rat: Alterations of IL-10 Expression in Radiation-induced Lung Damage

Concise Review: Therapeutic Potential of the Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Radiation-Induced Lung Injury: Progress and Hypotheses

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