Effect of α- and δ-Tocotrienol on Human Airway Smooth Muscle Cells~Tocotrienols as Potential Candidates for the Treatment of Airway Remodeling in Asthma

抄録

Tocotrienols are members of the vitamin E family and exhibit antioxidant properties, immunomodulatory effects, and anti-inflammatory actions. Previously, we demonstrated that γ-tocotrienol inhibits human airway smooth muscle (ASM) cell proliferation, migration, contractile phenotype expression, and extracellular matrix protein synthesis by suppressing RhoA activation. In this study, we investigated whether α- or δ-tocotrienol modulates transforming growth factor-beta 1 (TGF-β1)–induced contractile phenotype expression in human ASM cells and platelet-derived growth factor-BB (PDGF-BB)–induced proliferation and migration of ASM cells. Human ASM cells were pretreated with α- or δ-tocotrienol before stimulation with PDGF-BB to promote proliferation and migration or with TGF-β1 to induce smooth muscle actin expression. PDGF-BB–stimulated ASM cell proliferation and migration were assessed using colorimetric and transwell migration assays. Additionally, we examined the signaling pathways involved in the effects of α- or δ-tocotrienol on PDGF-BB–induced ASM proliferation and migration, as well as TGF-β1–induced smooth muscle actin expression. TGF-β1 increased α-smooth muscle actin expression in human ASM cells. Treatment with α- and δ-tocotrienol slightly reduced α-smooth muscle actin levels, though this reduction was not statistically significant. In contrast, PDGF-BB–induced ASM cell proliferation and migration were significantly inhibited by α- and δ-tocotrienol treatment. The effects of α- and δ-tocotrienol on ASM proliferation and migration involve the RhoA signaling pathway and a reduction in reactive oxygen species (ROS) production. These findings suggest that α- and δ-tocotrienol exert beneficial effects on airway remodeling in asthma by inhibiting the proliferation and migration of human ASM cells.