Asbestos induces tissue factor in Beas-2B cells via PI3 kinase-PKC-mediated signaling.
Treatment of Beas-2B airway epithelial cells with crocidolite asbestos induced tissue factor (TF) mRNA and TF-dependent procoagulant activity. The mitogen-activated protein kinase (MAPK) inhibitors UO126 and SB203850 decreased TF expression in both naive and crocidolite-treated Beas-2B cells to the same extent. Calphostin, an inhibitor of classical and novel protein kinase C (PKC) isotypes, reduced TF mRNA in both intact and crocidolite-treated Beas-2B cells by about 50%. Conversely, the phosphatidylinositol 3-kinase (PI3 kinase) inhibitor LY294002 and a selective PKCzeta inhibitory peptide decreased TF mRNA expression in asbestos-treated cells to a greater extent than in naive cells, suggesting that signaling via this pathway contributes to asbestos-induced TF expression. These results demonstrate that crocidolite asbestos induces TF expression by Beas-2B cells and suggest that the process involves the PI3 kinase-PKCzeta signaling pathway, representing a newly recognized potential mechanism by which asbestos may contribute to lung remodeling.
Iakhiaev
Alexei
A
Department of Specialty Care Services, University of Texas Health Center at Tyler, Tyler, Texas 75708, USA. alexei.iakhiaev@uthct.edu
Idell
Steven
S
D017638:Asbestos, Crocidolite / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D005170:Factor X / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D020545:Respiratory Mucosa / Q000502:physiology; D015398:Signal Transduction; D013925:Thromboplastin / Q000187:drug effects* / Q000502:physiology
D002273:Carcinogens; D017638:Asbestos, Crocidolite; D005170:Factor X; D013925:Thromboplastin; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases