Interleukin-6-mediated trans-signaling inhibits transforming growth factor-β signaling in trabecular meshwork cells

The Journal of Biological Chemistry
Miyuki Inoue-MochitaHidenobu Tanihara

Abstract

Glaucoma is one of the major causes of blindness, and transforming growth factor-β2 (TGF-β2) has been found to be elevated in the aqueous humor of eyes with primary open-angle glaucoma (POAG). TGF-β2 in aqueous humor causes the glaucoma-related fibrosis of human trabecular meshwork (HTM), suggesting an important role of TGF-β in POAG pathogenesis. Here, we sought to elucidate the effects of IL-6 trans-signaling on TGF-β signaling in HTM cells. Using a multiplex immunoassay, POAG patients decreased IL-6 levels and increased soluble IL-6 receptor (sIL-6R) levels compared with the controls. In in vitro experiments, we observed that the IL-6 level was increased in the conditioned medium of HTM cells after TGF-β2 stimulation. To elucidate the relationship between TGF-β2 and IL-6 in HTM cells, we conducted Western blotting and immunohistochemical analyses, and we noted that the combination of IL-6 and sIL-6R (IL6/sIL-6R) suppressed TGF-β-induced up-regulation of α-smooth muscle actin in HTM cells, whereas IL-6 alone did not. This suggests that trans-signaling, not classic signaling, of IL-6 suppresses TGF-β-induced fibrosis of HTM. IL6/sIL-6R also suppressed TGF-β-mediated activation of myosin light chain 2 (MLC2), Smad2, and p38. Of...Continue Reading

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Citations

May 12, 2020·American Journal of Physiology. Renal Physiology·Sarika ChaudhariRong Ma
Nov 12, 2020·Journal of Clinical Medicine·Sergio Claudio SaccàAnna Maria Bassi
Nov 21, 2020·Investigative Ophthalmology & Visual Science·Felix Yemanyi, VijayKrishna Raghunathan
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Aug 14, 2021·European Journal of Ophthalmology·Zulvikar Syambani UlhaqMuhammad A'raaf Sirojan Kusuma
May 18, 2020·Archivos de la Sociedad Española de Oftalmología·Z S Ulhaq, G V Soraya

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