PMID- 27231521 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160527 LR - 20210109 IS - 1949-8462 (Print) IS - 1949-8462 (Electronic) VI - 8 IP - 5 DP - 2016 May 26 TI - Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4. PG - 340-50 LID - 10.4330/wjc.v8.i5.340 [doi] AB - 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 mumol/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 mumol/L, 24 h). The expression of the pro-inflammatory cytokines; interleukin (IL)-6, IL-1beta, TNFalpha 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. FAU - Maqbool, Azhar AU - Maqbool A AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Spary, Emma J AU - Spary EJ AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Manfield, Iain W AU - Manfield IW AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Ruhmann, Michaela AU - Ruhmann M AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Zuliani-Alvarez, Lorena AU - Zuliani-Alvarez L AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Gamboa-Esteves, Filomena O AU - Gamboa-Esteves FO AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Porter, Karen E AU - Porter KE AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Drinkhill, Mark J AU - Drinkhill MJ AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Midwood, Kim S AU - Midwood KS AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Turner, Neil A AU - Turner NA AD - Azhar Maqbool, Emma J Spary, Karen E Porter, Mark J Drinkhill, Neil A Turner, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom. LA - eng GR - 20003/VAC_/Versus Arthritis/United Kingdom PT - Journal Article PL - United States TA - World J Cardiol JT - World journal of cardiology JID - 101537090 PMC - PMC4877363 OTO - NOTNLM OT - Cardiac fibroblasts OT - Interleukin-6 OT - Matrix metalloproteinase OT - Tenascin C OT - Toll-like receptor EDAT- 2016/05/28 06:00 MHDA- 2016/05/28 06:01 PMCR- 2016/05/26 CRDT- 2016/05/28 06:00 PHST- 2016/03/03 00:00 [received] PHST- 2016/04/04 00:00 [revised] PHST- 2016/04/14 00:00 [accepted] PHST- 2016/05/28 06:00 [entrez] PHST- 2016/05/28 06:00 [pubmed] PHST- 2016/05/28 06:01 [medline] PHST- 2016/05/26 00:00 [pmc-release] AID - 10.4330/wjc.v8.i5.340 [doi] PST - ppublish SO - World J Cardiol. 2016 May 26;8(5):340-50. doi: 10.4330/wjc.v8.i5.340.