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Effects of lysophosphatidic acid and its receptors LPA⅓ on radiation pneumonitis.
- Source :
-
Oncology reports [Oncol Rep] 2010 Dec; Vol. 24 (6), pp. 1515-20. - Publication Year :
- 2010
-
Abstract
- Radiation pneumonitis (RP) is a serious complication of radiation therapy for thoracic tumors. Lysophosphatidic acid (LPA) and its receptors LPA⅓ were reported to participate in the processes of inflammation. We tested the hypothesis that LPA and its receptors LPA⅓, take part in the pathogenesis of RP. In our study, irradiation increased LPA levels in the lung and expression of LPA⅓. To further determine the role of LPA⅓, we performed pharmacological knockout of LPA⅓ by a specific antagonist, VPC-12249. On day 60 post-irradiation, RP was significantly alleviated in a dose-dependent manner in mice treated with VPC-12249, as shown by H&E staining, malondialdehyde (MDA, an indicator of oxidative damage) assay in lung, and concentrations of proinflammatory and profibrotic cytokines in plasma, including IL-1β, TNF-α, and TGF-β1. Additionally, VPC-12249 administration decreased the phosphorylation of IκB-α (the initial event that activates the NF-κB signal way), and expression of TGF-β1, CTGF, and α-SMA mRNA. Our findings suggest that LPA and LPA⅓ may play a pivotal role in RP, and LPA-LPA⅓ may serve as novel therapeutic targets for the treatment of RP.
- Subjects :
- Animals
Connective Tissue Growth Factor genetics
Connective Tissue Growth Factor metabolism
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Female
I-kappa B Kinase genetics
I-kappa B Kinase metabolism
Lung drug effects
Lung metabolism
Lung pathology
Lysophospholipids metabolism
Mice
Mice, Inbred C57BL
Oleic Acids administration & dosage
Oleic Acids pharmacology
Oleic Acids therapeutic use
Organophosphates administration & dosage
Organophosphates pharmacology
Organophosphates therapeutic use
Phosphorylation drug effects
Radiation Pneumonitis metabolism
Radiation-Protective Agents administration & dosage
Radiation-Protective Agents pharmacology
Radiation-Protective Agents therapeutic use
Receptors, Lysophosphatidic Acid metabolism
Transforming Growth Factor beta1 genetics
Transforming Growth Factor beta1 metabolism
Lysophospholipids pharmacology
Radiation Pneumonitis drug therapy
Radiation Pneumonitis etiology
Receptors, Lysophosphatidic Acid antagonists & inhibitors
Receptors, Lysophosphatidic Acid physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 21042747
- Full Text :
- https://doi.org/10.3892/or_00001013