Combined Tlr2 and Tlr4 Deficiency Increases Radiation-Induced Pulmonary Fibrosis in Mice

Journal Article · Thu Jul 15 04:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.12.065· OSTI ID:21436093

Paun, Alexandra ^[1]; Fox, Jessica ^[2]; Balloy, Viviane; Chignard, Michel ^[3]; Qureshi, Salman T ^[2]

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1. Department of Human Genetics, McGill University, Montreal, QC (Canada)
2. Department of Medicine and the Meakins-Christie Laboratories, McGill University, Montreal, QC (Canada)
3. Institut Pasteur, Unite de Defense innee et Inflammation, Inserm, Paris (France)

Purpose: To determine whether Toll-like receptor 2 or 4 genotype alters the lung response to irradiation in C57BL/6 mice using a model developing a phenotype that resembles radiotherapy-induced fibrosis in both histological characteristics and onset post-treatment. Methods and Materials: The pulmonary phenotype of C57BL/6 mice deficient in each or both of these genes was assessed after an 18-Gy single dose to the thoracic cavity by survival time postirradiation, bronchoalveolar lavage cell differential, histological evidence of alveolitis and fibrosis, and gene expression levels, and compared with that of wild-type mice. Results: The lung phenotype of Tlr4-deficient and Tlr2-deficient mice did not differ from that of wild-type mice in terms of survival time postirradiation, or by histological evidence of alveolitis or fibrosis. In contrast, mice deficient in both receptors developed respiratory distress at an earlier time than did wild-type mice and presented an enhanced fibrotic response (13.5% vs. 5.8% of the lung by image analysis of histological sections, p < 0.001). No differences in bronchoalveolar cell differential counts, nor in numbers of apoptotic cells in the lung as detected through active caspase-3 staining, were evident among the irradiated mice grouped by Tlr genotype. Gene expression analysis of lung tissue revealed that Tlr2,4-deficient mice have increased levels of hyaluronidase 2 compared with both wild-type mice and mice lacking either Tlr2 or Tlr4. Conclusion: We conclude that a combined deficiency in both Tlr2 and Tlr4, but not Tlr2 or Tlr4 alone, leads to enhanced radiation-induced fibrosis in the C57BL/6 mouse model.

• OSTI ID: 21436093
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 4 Vol. 77; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
APOPTOSIS
BODY
FIBROSIS
GENES
GENOTYPE
IMAGE PROCESSING
LUNGS
MAMMALS
MEDICINE
MEMBRANE PROTEINS
MICE
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PHENOTYPE
PROCESSING
PROTEINS
RADIOLOGY
RADIOTHERAPY
RECEPTORS
RESPIRATORY SYSTEM
RODENTS
SURVIVAL TIME
THERAPY
VERTEBRATES