Radiation produces differential changes in cytokine profiles in radiation lung fibrosis sensitive and resistant mice

Ao, Xiaoping; Zhao, Lujun; Davis, Mary A.; Lubman, David M.; Lawrence, Theodore S.; Kong, Feng-Ming

doi:10.1186/1756-8722-2-6

Cited by 92 publications

(88 citation statements)

References 39 publications

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“…54 ROS produced by ischemia/reperfusion injury significantly increased the mRNA expression of MCP-1/CCL2 in the heart, 55 as has also been shown for the hepatotoxin carbon tetrachloride, 56 as well as whole lung irradiation in mice. 57 IL-8/CXCL8 has been considered to be of crucial importance for recruitment of granulocytes in different tissues. 7 In previous work, 25 however, we were surprised to find a massive up-regulation of CXCL8 gene expression in the liver of rats treated with turpentine oil intramuscularly without detecting any granulocyte infiltration.…”

Section: Discussionmentioning

confidence: 99%

Single-Dose Gamma-Irradiation Induces Up-Regulation of Chemokine Gene Expression and Recruitment of Granulocytes into the Portal Area but Not into Other Regions of Rat Hepatic Tissue

Malik

Moriconi

Sheikh

et al. 2010

The American Journal of Pathology

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Liver damage is a serious clinical complication of ␥-irradiation. We therefore exposed rats to singledose ␥-irradiation (25 Gy) that was focused on the liver. Three to six hours after irradiation, an increased number of neutrophils (but not mononuclear phagocytes) was observed by immunohistochemistry to be attached to portal vessels between and around the portal (myo)fibroblasts (smooth muscle actin and Thy-1 ؉ cells). MCP-1/CCL2 staining was also detected in the portal vessel walls , including some cells of the portal area. CC-chemokine (MCP-1/CCL2 and MCP-3/CCL7) and CXC-chemokine (KC/CXCL1, MIP-2/CXCL2, and LIX/CXCL5) gene expression was significantly induced in total RNA from irradiated livers. In laser capture microdissected samples, an early (1 to 3 hours) up-regulation of CCL2, CXCL1, CXCL8, and CXCR2 gene expression was detected in the portal area but not in the parenchyma; with the exception of CXCL1 gene expression. In addition, treatment with an antibody against MCP-1/CCL2 before irradiation led to an increase in gene expression of interferon-␥ and IP-10/CXCL10 in liver tissue without influencing the recruitment of granulocytes. Indeed, the CCL2, CXCL1, CXCL2, and CXCL5 genes were strongly expressed and further up-regulated in liver (myo)fibroblasts after irradiation (8 Gy). Taken together, these results suggest that ␥-irradiation of the liver induces a transient accumulation of granulocytes within the portal area and that (myo)fibroblasts of the portal vessels may be one of the major sources of the chemokines involved in neutrophil recruitment. Moreover, inhibition of more than one chemokine (eg, CXCL1 and CXCL8) may be necessary to reduce leukocytes recruitment.

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Section: Discussionmentioning

confidence: 99%

Single-Dose Gamma-Irradiation Induces Up-Regulation of Chemokine Gene Expression and Recruitment of Granulocytes into the Portal Area but Not into Other Regions of Rat Hepatic Tissue

Malik

Moriconi

Sheikh

et al. 2010

The American Journal of Pathology

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“…After a single-dose thoracic irradiation, the time of pneumonitis occurrence and changes of the TNF-a mRNA and protein levels in the irradiated lung have been shown to depend on the irradiation dose (Johnston et al 1998). As shown by Rube et al (2004); Ao et al (2009), following 20 Gy irradiation, the dose used also in our study, the expression of mRNA for TNF-a in the whole lung tissue increases with time in a bimodal fashion, peaking at 1 h and at the 2nd month. In addition, markedly increased TNF-a mRNA levels observed 1 h after irradiation decline within 48 h.…”

Section: Time After Irradiation (Weeks)mentioning

confidence: 99%

“…To investigate antifibrotic effects of systemic gene therapy, we chose a special, fibrosis-prone C57Bl/6J mice strain, with a well-documented lung TNF-a level alteration following irradiation (Ao et al 2009;Rube et al 2004). After a single-dose thoracic irradiation, the time of pneumonitis occurrence and changes of the TNF-a mRNA and protein levels in the irradiated lung have been shown to depend on the irradiation dose (Johnston et al 1998).…”

Section: Time After Irradiation (Weeks)mentioning

confidence: 99%

Soluble TNF-α Receptor I Encoded on Plasmid Vector and Its Application in Experimental Gene Therapy of Radiation-Induced Lung Fibrosis

Przybyszewska

Miłoszewska

Rzońca

et al. 2011

Arch. Immunol. Ther. Exp.

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Post-radiation inflammatory reaction leads to an irreversible pulmonary fibrosis which may cause lethal respiratory insufficiency. Pathological inflammatory and fibrotic changes might be attenuated by inhibiting tumour necrosis factor (TNF)-α activity using TNF-α soluble receptors. Thus, an experimental antifibrotic gene therapy with the plasmid vector encoding a mouse soluble receptor I for TNF-α (psTNFR-I) was assessed. Soluble TNFR-I encoding gene was cloned into pcDNA3.1 plasmid. The ability of psTNFR-I expressing vector to transfect cells, and its biological activity in vitro and in vivo were examined by PCR, RT-PCR, MTT assay and ELISA. The C57Bl/6J mice received single intramuscular injection of psTNFR-I, conjugated with polyetylenimine (PEI) 25 kDa, equally divided to both hind legs, 3 days before irradiation (20 Gy, Co60), and either a single injection or ten injections once a week after irradiation. The data proved the effectiveness of psTNFR-I product to neutralise TNF-α activity in vitro. The in vivo plasmid incorporation and maintenance was confirmed. Measurements of plasma soluble TNFR-I levels showed that the in vivo gene transfer was effective. PEI was found to enhance transfection efficiency in vivo. The psTNFR-I/PEI complexes caused no toxicity in the transfected mice. C57Bl/6J mice that received prolonged psTNFR-I/PEI injections developed lethal fibrotic syndrome and died 8 weeks later than the mice treated with a double plasmid injection and the control mice treated with a control plasmid. Sequential administration of soluble TNFR-I by a nonviral, intramuscular gene transduction in the early and late post-radiation inflammatory phase prolonged survival of irradiated mice and attenuated the symptoms of lung fibrosis. The psTNFR-I gene transduction may provide a safe and simple method to partially neutralise TNF-α activity and prevent radiation-induced lung injury.

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“…TGF-beta is accepted to be the dominant profibrotic cytokine, and it can even be the cause of RP. Therefore, the interventions are for developing molecules with anti-TGF beta activity (83)(84)(85). The use of keratinocyte growth factor in mucositis developing in bone marrow transplantation is approved by the American Food and Drug Administration (FDA), and its preclinical trials have been continuing for RF (86).…”

Section: Prevention Of Lung Injury Associated With Radiationmentioning

confidence: 99%

Pulmonary Toxicities and Treatment of Radiation Therapy

Argüder¹,

Yıldırım²,

Hasanoğlu³

2015

Eurasian J Pulmonol

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Radiotherapy (RT), used for the treatment of cancers, such as lung cancer, lymphoma, breast cancer, bone marrow transplantation, and esophageal cancer, causes the exposure of lungs to radiation. Since the lungs are very sensitive to ionizing radiation, radiation-induced lung diseases due to radiation therapy are usually common. In this article, lung diseases secondary to RT and the diagnosis and treatment of these diseases were evaluated in light of the literature.Keywords: Cancer, lung, radiotherapy, toxicity INTRODUCTIONThe exposure of normal tissues, besides cancerous tissues, to radiation from the first days of radiotherapy (RT) application has been an important limiting factor. Although the incidence of radiation-induced normal tissue injury has diminished with the development of radiation oncology technology in recent years, it still goes on. In this review, general information about RT is given, and RT-induced toxicity types that develop in the lungs and therapies are explained. GENERAL INFORMATIONRT is used for palliative, curative, adjuvant, and prophylactic purposes in cancer treatment. The aim during radiotherapy application is to reduce or remove tumor load while protecting normal tissue. The injury of normal tissue always poses the main obstacle to RT. In time, strategies, such as dose-volume modulation, image-guided RT applications, involved-field radiotherapy, and the use of lung disease-preventive agents, have been developed to overcome this problem Thoracic RT may be conducted in cases, such as lung cancer, bone marrow transplantation, and esophageal cancer. Lungs are among the most sensitive organs to ionizing radiation, and this sensitivity is one of the most important dose-limiting obstacles of thoracic RT. Temporary sequential inflammatory events are seen in the lung tissue as a response to radiation exposure. Here, individual differences, by affecting the outcome, bring about the occurrence of normal or pathological responses. Radiation-induced lung injury is a progressive process, including inflammation and repair. The development of injury may be prevented and the development of new strategies for treatment may be possible by understanding the underlying mechanisms of the basic molecular damage caused by radiotherapy (1, 2).Today, external RT (EBRT), brachytherapy, intraoperative RT (IORT), stereotactic RT (SRT), three-dimensional conformal RT (3D-CRT), intensity-modulated RT (IMRT), image-guided RT (IGRT), tomotherapy, cyberknife (robotic radiosurgery), boron neutron capture therapy, and hyperthermia are among RT applications. Location of the tumor, its histopathological feature, sensitivity to RT, the patient's undergoing surgical intervention, and his receiving chemotherapy are important for the preference of the appropriate technique (3). 150Radiation has an impact on the alveolocapillary unit of the lung according to the proliferation of cells. Endothelial, epithelial (particularly, type 2 pneumocytes producing surfactant), and reticuloendothelial system cells are more sensi...

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Radiation produces differential changes in cytokine profiles in radiation lung fibrosis sensitive and resistant mice

Abstract: Background: Recent research has supported that a variety of cytokines play important roles during radiation-induced lung toxicity. The present study is designed to investigate the differences in early cytokine induction after radiation in sensitive (C57BL/6) and resistant mice (C3H).

Cited by 92 publications

References 39 publications

Single-Dose Gamma-Irradiation Induces Up-Regulation of Chemokine Gene Expression and Recruitment of Granulocytes into the Portal Area but Not into Other Regions of Rat Hepatic Tissue

Single-Dose Gamma-Irradiation Induces Up-Regulation of Chemokine Gene Expression and Recruitment of Granulocytes into the Portal Area but Not into Other Regions of Rat Hepatic Tissue

Soluble TNF-α Receptor I Encoded on Plasmid Vector and Its Application in Experimental Gene Therapy of Radiation-Induced Lung Fibrosis

Pulmonary Toxicities and Treatment of Radiation Therapy

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