IL-13 is a therapeutic target in radiation lung injury
| Autor: | Eun Joo Chung, Deborah Citrin, Ayla O. White, Jason A. Horton, Thirumalai R. Ramalingam, Su I. Chung, Bradley T. Scroggins, Joseph R. Arron, Thomas A. Wynn, Kathryn E. Hudak |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pulmonary Fibrosis Disease Lung injury Article 03 medical and health sciences Mice 0302 clinical medicine Immune system Fibrosis Pulmonary fibrosis medicine Animals Receptor Adverse effect Mice Knockout Multidisciplinary Interleukin-13 business.industry Lung Injury medicine.disease Radiation Injuries Experimental 030104 developmental biology 030220 oncology & carcinogenesis Interleukin 13 Cancer research business |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Pulmonary fibrosis is a potentially lethal late adverse event of thoracic irradiation. Prior research indicates that unrestrained TGF-β1 and/or type 2 cytokine-driven immune responses promote fibrosis following radiation injury, but the full spectrum of factors governing this pathology remains unclear. Interleukin 13 (IL-13) is a key factor in fibrotic disease associated with helminth infection, but it is unclear whether it plays a similar role in radiation-induced lung fibrosis. Using a mouse model, we tested the hypothesis that IL-13 drives the progression of radiation-induced pulmonary fibrosis. Irradiated lungs from wild-type c57BL/6NcR mice accumulated alternatively-activated macrophages, displayed elevated levels of IL-13, and extensive fibrosis, whereas IL-13 deficient mice were resistant to these changes. Furthermore, plasma from irradiated wild-type mice showed a transient increase in the IL-13 saturated fraction of the circulating decoy receptor IL-13Rα2. Finally, we determined that therapeutic neutralization of IL-13, during the period of IL-13Rα2 saturation was sufficient to protect mice from lung fibrosis. Taken together, our results demonstrate that IL-13 is a major regulator of radiation-induced lung injury and demonstrates that strategies focusing on IL-13 may be useful in screening for timely delivery of anti-IL-13 therapeutics. |
| Databáze: | OpenAIRE |
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