The role of the receptor for advanced glycation end-products in a murine model of silicosis
| Autor: | Jacob M. Tobolewski, Adriana S. Leme, Jan J. Enghild, A. Murat Kaynar, Tim D. Oury, Steven D. Shapiro, Cheryl L. Fattman, Lauren Tomai, Judson M. Englert, Lasse Ramsgaard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Glycation End Products
Advanced Pathology endocrine system diseases Pulmonary Fibrosis Receptor for Advanced Glycation End Products lcsh:Medicine RAGE (receptor) chemistry.chemical_compound Mice 0302 clinical medicine Respiratory Medicine/Interstitial Lung Diseases Fibrosis Transforming Growth Factor beta Pulmonary fibrosis Medicine Receptors Immunologic lcsh:Science Lung Mice Knockout 0303 health sciences Multidisciplinary respiratory system 3. Good health Hydroxyproline medicine.anatomical_structure Physiology/Respiratory Physiology medicine.symptom Bronchoalveolar Lavage Fluid Research Article medicine.medical_specialty Public Health and Epidemiology/Environmental Health Silicosis Inflammation Bleomycin 03 medical and health sciences Animals 030304 developmental biology business.industry lcsh:R medicine.disease Mice Inbred C57BL Disease Models Animal 030228 respiratory system chemistry Gene Expression Regulation lcsh:Q business |
| Zdroj: | Ramsgaard, L, Englert, J M, Tobolewski, J, Tomai, L, Fattman, C L, Leme, A S, Kaynar, A M, Shapiro, S D, Enghild, J J & Oury, T D 2010, ' The role of the receptor for advanced glycation end-products in a murine model of silicosis ', P L o S One, vol. 5, no. 3, pp. e9604 . https://doi.org/10.1371/journal.pone.0009604 PLoS ONE, Vol 5, Iss 3, p e9604 (2010) PLoS ONE |
| DOI: | 10.1371/journal.pone.0009604 |
| Popis: | Udgivelsesdato: 2010-null BACKGROUND: The role of the receptor for advanced glycation end-products (RAGE) has been shown to differ in two different mouse models of asbestos and bleomycin induced pulmonary fibrosis. RAGE knockout (KO) mice get worse fibrosis when challenged with asbestos, whereas in the bleomycin model they are largely protected against fibrosis. In the current study the role of RAGE in a mouse model of silica induced pulmonary fibrosis was investigated. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT) and RAGE KO mice received a single intratracheal (i.t.) instillation of silica in saline or saline alone as vehicle control. Fourteen days after treatment mice were subjected to a lung mechanistic study and the lungs were lavaged and inflammatory cells, protein and TGF-beta levels in lavage fluid determined. Lungs were subsequently either fixed for histology or excised for biochemical assessment of fibrosis and determination of RAGE protein- and mRNA levels. There was no difference in the inflammatory response or degree of fibrosis (hydroxyproline levels) in the lungs between WT and RAGE KO mice after silica injury. However, histologically the fibrotic lesions in the RAGE KO mice had a more diffuse alveolar septal fibrosis compared to the nodular fibrosis in WT mice. Furthermore, RAGE KO mice had a significantly higher histologic score, a measure of affected areas of the lung, compared to WT silica treated mice. A lung mechanistic study revealed a significant decrease in lung function after silica compared to control, but no difference between WT and RAGE KO. While a dose response study showed similar degrees of fibrosis after silica treatment in the two strains, the RAGE KO mice had some differences in the inflammatory response compared to WT mice. CONCLUSIONS/SIGNIFICANCE: Aside from the difference in the fibrotic pattern, these studies showed no indicators of RAGE having an effect on the severity of pulmonary fibrosis following silica injury. |
| Databáze: | OpenAIRE |
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