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. 2017 May 25;7:2415. doi: 10.1038/s41598-017-02611-5

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Inflammation drives ZIP-8 and MT-s mediated Cd absorption and accumulation in synoviocytes, inducing apoptosis and reducing IL-6 production. (A) Cell viability of OA and RA synoviocyte cultures assessed by neutral red assay at day 1, 5 and 8 after exposure to Cd. (B) Annexin V staining of OA and RA synoviocytes exposed or not to Cd for 5 days in the presence or not of IL-17 and TNF. (C) IL-6 production of OA and RA synoviocyte cultures assessed by ELISA assay at day 8 after exposure to Cd. (D) Cd concentration in medium as function of time and in synoviocyte culture at 120 hours. Gray dashed line: control experiment with no cytokine addition. Black line: Cd plus IL-17 and TNF condition. Vertical dashed line at 48 hours: washing. (E) Gene expression of Cd transporters in comparison to GAPDH. Black bars and lines: exposure to Cd. Data are the mean of at least three independent cell lines/biopsies (from three independent patients). Data are represented as mean ± SEM; *shows differences between non-inflammatory and inflammatory conditions, ^#shows differences due to Cd addition; *^/#p < 0.05, **^/##p < 0.01.