title: The functional expression of TLR3 in EPCs impairs cell proliferation by induction of cell apoptosis and cell cycle progress inhibition.
abstract: Toll-like receptor 3 (TLR3), a member of the TLR family that recognizes double-stranded RNA (dsRNA), plays an important role in antiviral immunity. TLR3 is widely expressed in various cells and the activation of TLR3 induces cell apoptosis in some cells. However, the effect of TLR3 on cell proliferation in endothelial progenitor cells (EPCs) is unclear. In this study, we found that EPCs expressed high levels of TLR1, 3, 4, and 6 and low levels of TLR2, 5, 7, 8, and 10. The treatment of EPCs with TLR3 agonist Poly I:C up-regulated the expression of cytokines IL-1β, IL-6, IL-8, TNF-α, IFN-α, and IFN-β, indicating that EPCs expressed functional TLR3. Moreover, Poly I:C treatment induced cell cycle progress inhibition and cell apoptosis, leading to the inhibition of cell proliferation. Further studies indicated that IL-1β was involved in TLR3-induced cell proliferation inhibition, as IL-1β inhibited cell proliferation in a dose-dependent manner, and the IL-1β receptor type I (IL-1R1)-neutralizing antibody ameliorated Poly I:C-induced cell proliferation inhibition. Taken together, these results suggest that Poly I:C impairs cell proliferation by inducing cell cycle progress inhibition and cell apoptosis via TLR3 in EPCs.
authors.affiliation: Department of Geriatric Cardiology, Xiangya Hospital,Central South University, Changsha, 410008, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Xiao
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Lv
authors.forename: Xueting
authors.initials: X
authors.lastname: Liu
authors.forename: Lina
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Chen
authors.forename: Meifang
authors.initials: M
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Xie
authors.forename: Jinyue
authors.initials: J
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D011070:Poly I-C / Q000494:pharmacology; D053573:Receptors, Interleukin-1 Type I / Q000037:antagonists & inhibitors; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000096:biosynthesis*; D051193:Toll-Like Receptors / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; C508590:IL1R1 protein, human; D053573:Receptors, Interleukin-1 Type I; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D011070:Poly I-C