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Annexin A5 promotes macrophage activation and contributes to pulmonary fibrosis induced by silica particles.
- Source :
-
Toxicology and industrial health [Toxicol Ind Health] 2016 Sep; Vol. 32 (9), pp. 1628-38. Date of Electronic Publication: 2015 Mar 10. - Publication Year :
- 2016
-
Abstract
- Objective: To investigate the contributions and underlying molecular mechanisms of annexin A5 toward silica-induced pulmonary fibrosis.<br />Methods: Male C57BL/6 mice were randomly divided into three groups and instilled intratracheally with silica, saline, or air. Mice were euthanized at 3, 7, 14, or 28 days following treatment. Annexin A5 levels in serum and lung tissues were detected by enzyme-linked immunosorbant assay (ELISA) assays or Western blots. The association of annexin A5 levels with silica-induced lung fibrosis was further investigated in the macrophage cell line, RAW264.7. Following exposure of these cells to silica at a concentration of 200 μg/ml for 6 or 12 h, the expression levels of transforming growth factor β1 (TGF-β1), interleukin 1α (IL-1α), Fas ligand (FasL), and their downstream targets were evaluated by Western blots. Furthermore, annexin A5 and FasL were knocked down by small interfering ribonucleic acid (siRNA) and TGF-β1 secretion into the cell culture medium was measured by ELISA assays or Western blots.<br />Results: Mice treated with silica demonstrated lung fibrosis at 28 days following exposure, whereas, in controls, only mild and transient inflammation was evident at day 3 and day 7 postinstillation and was not present at day 14. Furthermore, silica-exposed mice exhibited significantly (p < 0.05) elevated levels of annexin A5 in serum and lung tissues, relative to control groups. Consistent with these findings, silica exposure of RAW264.7 cells for 6 or 12 h, led to an annexin A5-dependent increase in the expression levels of TGF-β1, IL-1α, FasL, and their downstream target molecules. These silica-induced changes were reversed by siRNA-mediated knockdown of annexin A5, but downregulation of FasL led to increased annexin A5 expression and reduced levels of TGF-β1, IL-1α, and FasL downstream target molecules.<br />Conclusions: These findings define a role of annexin A5 in promoting macrophage activation via Fas/FasL pathways in silica-induced lung fibrosis.<br /> (© The Author(s) 2015.)
- Subjects :
- Air Pollutants chemistry
Air Pollutants toxicity
Animals
Annexin A5 antagonists & inhibitors
Annexin A5 blood
Annexin A5 genetics
Cytokines agonists
Cytokines metabolism
Fas Ligand Protein antagonists & inhibitors
Fas Ligand Protein genetics
Fas Ligand Protein metabolism
Lung drug effects
Lung immunology
Lung metabolism
Lung pathology
Macrophages drug effects
Macrophages immunology
Macrophages metabolism
Male
Mice
Mice, Inbred C57BL
Particulate Matter chemistry
Particulate Matter toxicity
RAW 264.7 Cells
RNA Interference
Random Allocation
Respiratory Mucosa immunology
Respiratory Mucosa metabolism
Respiratory Mucosa pathology
Signal Transduction drug effects
Silicon Dioxide chemistry
Silicosis immunology
Silicosis metabolism
Silicosis pathology
Specific Pathogen-Free Organisms
Annexin A5 metabolism
Disease Models, Animal
Macrophage Activation drug effects
Pulmonary Fibrosis etiology
Respiratory Mucosa drug effects
Silicon Dioxide toxicity
Silicosis physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1477-0393
- Volume :
- 32
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Toxicology and industrial health
- Publication Type :
- Academic Journal
- Accession number :
- 25757482
- Full Text :
- https://doi.org/10.1177/0748233715572744