[HTML][HTML] TGF-β-induced interleukin-6 participates in transdifferentiation of human Tenon's fibroblasts to myofibroblasts

GJ Seong, S Hong, SA Jung, JJ Lee, E Lim… - Molecular …, 2009 - ncbi.nlm.nih.gov
GJ Seong, S Hong, SA Jung, JJ Lee, E Lim, SJ Kim, JH Lee
Molecular vision, 2009ncbi.nlm.nih.gov
Purpose To gain a better understanding of the roles of interleukins (ILs) in subconjunctival
fibrosis, we investigated their expression in transforming growth factor-β1 (TGF-β1)-
stimulated Tenon's fibroblasts and examined their association with the transdifferentiation of
fibroblasts to myofibroblasts. Methods After primary culture, fibroblasts derived from human
Tenon's capsule were exposed to TGF-β1. The expression of α-smooth muscle actin (α-
SMA) protein was assessed by western immunoblots and immunofluorescence. The mRNA …
Abstract
Purpose
To gain a better understanding of the roles of interleukins (ILs) in subconjunctival fibrosis, we investigated their expression in transforming growth factor-β1 (TGF-β1)-stimulated Tenon’s fibroblasts and examined their association with the transdifferentiation of fibroblasts to myofibroblasts.
Methods
After primary culture, fibroblasts derived from human Tenon’s capsule were exposed to TGF-β1. The expression of α-smooth muscle actin (α-SMA) protein was assessed by western immunoblots and immunofluorescence. The mRNA levels of various ILs were also evaluated by multiplex reverse transcription (RT)-PCR. Using the small interfering RNAs (siRNAs) specific for IL-6 and IL-11 and the promoter deletion assay, the contributions of IL-6 and IL-11 to TGF-β1-induced induction of α-SMA were determined.
Results
In human Tenon’s fibroblasts, TGF-β1 stimulated the expression of α-SMA protein determined by western blot analysis and also increased the mRNA levels of IL-6 and IL-11 determined by multiplex RT-PCR. On the western immunoblots and immunofluorescence, the increased expression of α-SMA was attenuated only by the siRNAs specific for IL-6 but not by the siRNAs specific for IL-11. When the activator protein-1 binding sites of the IL-6 promoter region were deleted, the stimulation effects of TGF-β1 decreased.
Conclusions
Our data show that autocrine IL-6 may participate in the TGF-β1-induced transdifferentiation of human Tenon’s fibroblasts to myofibroblasts, which is known to be an essential step for subconjunctival fibrosis.
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