IL-13 overexpression in mouse lungs triggers systemic genotoxicity in peripheral blood
| Autor: | Aaron M. Chapman, Daniel Malkin, Jessica Camacho, Robert H. Schiestl |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Genetically modified mouse
DNA damage Health Toxicology and Mutagenesis Mice Transgenic Inflammation Biology medicine.disease_cause Article Transgenic Mice Th2 Cells Immune system Leukocytes Genetics medicine Animals 2.1 Biological and endogenous factors Oncology & Carcinogenesis Aetiology Lung Molecular Biology Asthma Interleukin-13 Animal medicine.disease Up-Regulation respiratory tract diseases Disease Models Animal medicine.anatomical_structure IL-13 Disease Models Interleukin 13 Immunology Respiratory Bone marrow Genotoxicity medicine.symptom DNA Damage |
| Zdroj: | Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 769:100-107 |
| ISSN: | 0027-5107 |
| DOI: | 10.1016/j.mrfmmm.2014.06.007 |
| Popis: | Asthma is a common heterogeneous disease with both genetic and environmental factors that affects millions of individuals worldwide. Activated type 2 helper T cells secrete a panel of cytokines, including IL-13, a central immune regulator of many of the hallmark type 2 disease characteristics found in asthma. IL-13 has been directly implicated as a potent stimulator of asthma induced airway remodeling. Although IL-13 is known to play a major role in the development and persistence of asthma, the complex combination of environmental and genetic origin of the disease obfuscate the solitary role of IL-13 in the disease. We therefore, used a genetically modified mouse model which conditionally overexpresses IL-13 in the lungs to study the independent role of IL-13 in the progression of asthma. Our results demonstrate IL-13 is associated with a systemic induction of genotoxic parameters such as oxidative DNA damage, single and double DNA strand breaks, micronucleus formation, and protein nitration. Furthermore we show that inflammation induced genotoxicity found in asthma extends beyond the primary site of the lung to circulating leukocytes and erythroblasts in the bone marrow eliciting systemic effects driven by IL-13 over-expression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect