title: The activation of TLR7 regulates the expression of VEGF, TIMP1, MMP2, IL-6, and IL-15 in Hela cells.
abstract: Toll-like receptors (TLRs) play important roles in activation of immunoreaction and tumor development. Toll-like receptor 7 (TLR7), one of the TLRs binding with single-stranded RNA, activates intracellular pathways and stimulates the release of proinflammatory cytokines, chemokines. In this study, we investigated the impact of the TLR7-signaling pathway on the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2), tissue inhibitor of metalloproteinase 1 (TIMP1), interleukin 6 (IL-6), and interleukin 15 (IL-15), which have been testified to refer to the immunomodulating and tumor progression. We confirmed that the TLR7 was expressed by Hela cells, despite the abundance was weak. Gardiquimod, one of the TLR7 ligands, can promote these five genes expression in varying degrees. After stimulating with gardiquimod, the expression of the IL-15V1, 3 increased about 4.5 times on RNA level, the other expression was only up-regulated about 2 times. We also discovered that gardiquimod could activate the MAPK/ERK- and PI3K/AKT-signaling pathways, and the specific inhibitors studies indicate that, the effect of gardiquimod on these genes expression is mainly or partially dependent on the activation of these two signaling pathways. To sum up, the activation of TLR7 signaling pathway may modulate some genes expression in Hela cells and may contribute to the pathogenesis of the cervical cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Feng-Wei
authors.initials: FW
authors.lastname: Cheng
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Jia
authors.forename: Xin
authors.initials: X
authors.lastname: Luo
authors.forename: Sheng-Quan
authors.initials: SQ
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D015870:Gene Expression / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D051199:Toll-Like Receptor 7 / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C569274:IL15 protein, human; D019409:Interleukin-15; D015850:Interleukin-6; C560822:TIMP1 protein, human; C495348:TLR7 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D051199:Toll-Like Receptor 7; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2