ABSTRACT
Sulfur mustard (SM) is a blister-forming agent and can cause damages in various momentous human organs. Previous studies have demonstrated that chemical and mechanical injuries of epithelial cells cause to give rise the secretion of TGF-ß1 and TGF-ß2. These cytokines play a key role in respiratory remodeling due to SM. In this study, we investigated the impact of SM on the expression level of TGF-ß isoforms and their receptors in vitro using reverse transcriptase polymerase chain reaction and western blotting. Our finding revealed the significant increase at concentrations of 25 µl/ml SM for 30 min and 60 min and also 100 µl/ml for 60 min for TGF-ß1, 25, 50 and 100 µl/ml SM for 30 min for TGF-ßr1 and after exposing with 100 µl/ml SM for both 30 and 60 min for TGF-ß2 (p < 0.05). Data from western blotting showed the increase of TGF-ß1 expression at the level of protein as the same pattern as the mRNA level. In vitro short-time exposure of fibroblast to SM can induce the expression of TGF-ß1, TGF-ß2 and TGF-ßR1 denoting that over-expression of TGF-ß isoforms and their receptors leads to differentiation and collagen production, causing in airway remodeling and fibrosis.
Subject(s)
Lung/drug effects , Lung/metabolism , Mustard Gas/toxicity , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta2/metabolism , Airway Remodeling/drug effects , Cell Line , Chemical Warfare Agents/toxicity , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Gene Expression/drug effects , Humans , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, Transforming Growth Factor-beta Type I , Receptors, Transforming Growth Factor beta/genetics , Receptors, Transforming Growth Factor beta/metabolism , Signal Transduction/drug effects , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta2/geneticsABSTRACT
The widespread use of sulfur mustard (SM) as a chemical warfare agent in the past century has proved its long-lasting toxic effects. Despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Transforming growth factor (TGF-ß), a cytokine that affects many different cell processes, has an important role in the lungs of patients with some of chronic airway diseases, especially with respect to airway remodeling in mustard lung. Primary airway fibroblasts from epibronchial biopsies were cultured, and gene expression of TGF-ß1, TGF-ß2, TbR-I and TbR-II in fibroblasts of SM injured patients and controls were investigated. Expression of TGF-ßs and receptors was measured by RT-PCR. Protein level of TGF-ß1 was surveyed by western blot. Our findings revealed that expression levels of TGF-ß1, TGF-ß2, TbR-I and TbR-II were upregulated in the airway fibroblasts of SM exposed patients in comparison with control samples. TGF-ß1 expression was shown to be markedly increased in primary lung fibroblasts of chemically injured patients. Our novel data, suggested that over-expression of TGF-ß molecule and receptors in primary airway fibroblasts of mustard gas injured patients may be involved in progression of airway remodeling of these patients.
