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Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4.

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. Green open access

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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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