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The activation of TLR7 regulates the expression of VEGF, TIMP1, MMP2, IL-6, and IL-15 in Hela cells

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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.

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Acknowledgments

This study was supported by the Grants from the General Program of National Natural Science Foundation of China (81271748), and the Foundation for Doctors, Anhui Medical University.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China

    Lei Li, Feng-Wei Cheng, Fang Wang, Bo Jia, Xin Luo & Sheng-Quan Zhang

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  1. Lei Li
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  2. Feng-Wei Cheng
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  3. Fang Wang
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  5. Xin Luo
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  6. Sheng-Quan Zhang
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Correspondence to Sheng-Quan Zhang.

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Li, L., Cheng, FW., Wang, F. et al. The activation of TLR7 regulates the expression of VEGF, TIMP1, MMP2, IL-6, and IL-15 in Hela cells. Mol Cell Biochem 389, 43–49 (2014). https://doi.org/10.1007/s11010-013-1925-y

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