Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro.
Asbestos has been implicated in the pathogenesis of interstitial lung diseases including asbestosis. Tissue factor (TF) initiates blood coagulation in vivo contributing to inflammation and tissue remodeling via extravascular fibrin deposition and signaling for profibrogenic mediators. We hypothesized that asbestos could induce TF expression by lung epithelial cells. We found that TF mRNA and TF-dependent procoagulant activity were induced in asbestos-treated Beas-2B human airway epithelial cells, which we used as a model system. The effect was increased by crocidolite and chrysotile versus control particulates, including titanium dioxide (TiO2) and Wollastonite (W). Transcription factors that bind the TF gene promoter, including NF-kappaB, AP1 and Sp1, were induced by asbestos while TF mRNA was unstable. TF mRNA was inhibited by mithramycin in asbestos-treated as well as control cells suggesting that Sp1 contributes to TF maintenance in Beas-2B cells. Sp1 knockdown with specific siRNA decreased TF antigen, which is consistent with Sp1-mediated control of TF in Beas-2B cells. The results demonstrate that asbestos induces TF expression in lung epithelial cells in vitro, representing a newly recognized potential mechanism by which asbestos may modulate epithelial cell responses germane to lung remodeling. The mechanism involves alterations in steady-state TF mRNA that do not involve posttranscriptional regulation, implicating control of TF gene expression at the transcriptional level through Sp1 or other transcription factors.
Iakhiaev
Alexei
A
Biomedical Research, The University of Texas Health Center at Tyler, Tyler, TX 75708, USA. Alexei.Iakhiaev@uthct.edu
Pendurthi
Usha
U
Idell
Steven
S
D001194:Asbestos / Q000633:toxicity*; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D012333:RNA, Messenger; D014157:Transcription Factors; D001194:Asbestos; D013925:Thromboplastin