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2016 ; 8
(5
): 340-50
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Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts
via toll-like receptor 4
#MMPMID27231521
Maqbool A
; Spary EJ
; Manfield IW
; Ruhmann M
; Zuliani-Alvarez L
; Gamboa-Esteves FO
; Porter KE
; Drinkhill MJ
; Midwood KS
; Turner NA
World J Cardiol
2016[May]; 8
(5
): 340-50
PMID27231521
show ga
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 ?mol/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 ?mol/L, 24 h). The expression of the
pro-inflammatory cytokines; interleukin (IL)-6, IL-1?, TNF? 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.
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