Maqbool, A;
Spary, EJ;
Manfield, IW;
Ruhmann, M;
Zuliani-Alvarez, L;
Gamboa-Esteves, FO;
Porter, KE;
... Turner, NA; + view all
(2016)
Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4.
World Journal of Cardiology
, 8
(5)
pp. 340-350.
10.4330/wjc.v8.i5.340.
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Abstract
AIM: To investigate the effect of Tenascin C (TNC) on the expression of pro-inflammatory cytokines and matrix metalloproteinases in human cardiac myofibroblasts (CMF). METHODS: CMF were isolated and cultured from patients undergoing coronary artery bypass grafting. Cultured cells were treated with either TNC (0.1 μmol/L, 24 h) or a recombinant protein corresponding to different domains of the TNC protein; fibrinogen-like globe (FBG) and fibronectin type III-like repeats (TNIII 5-7) (both 1 μmol/L, 24 h). The expression of the pro-inflammatory cytokines; interleukin (IL)-6, IL-1β, TNFα and the matrix metalloproteinases; MMPs (MMP1, 2, 3, 9, 10, MT1-MMP) was assessed using real time RT-PCR and western blot analysis. RESULTS: TNC increased both IL-6 and MMP3 (P < 0.01) mRNA levels in cultured human CMF but had no significant effect on the other markers studied. The increase in IL-6 mRNA expression was mirrored by an increase in protein secretion as assessed by enzyme-linked immunosorbant assay (P < 0.01). Treating CMF with the recombinant protein FBG increased IL-6 mRNA and protein (P < 0.01) whereas the recombinant protein TNIII 5-7 had no effect. Neither FBG nor TNIII 5-7 had any significant effect on MMP3 expression. The expression of toll-like receptor 4 (TLR4) in human CMF was confirmed by real time RT-PCR, western blot and immunohistochemistry. Pre-incubation of cells with TLR4 neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mRNA and protein expression. CONCLUSION: TNC up-regulates IL-6 expression in human CMF, an effect mediated through the FBG domain of TNC and via the TLR4 receptor.
| Type: | Article |
|---|---|
| Title: | Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.4330/wjc.v8.i5.340 |
| Publisher version: | http://dx.doi.org/10.4330/wjc.v8.i5.340 |
| Language: | English |
| Additional information: | This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved. Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
| Keywords: | Cardiac fibroblasts, Interleukin-6, Matrix metalloproteinase, Tenascin C, Toll-like receptor |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1517316 |
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