Effect of the IL-6 Trans-signaling Pathway in the Absence or Presence of TGF-β2 on Schlemm's Canal Endothelial Cells

Mai Urahashi; Tomokazu Fujimoto; Miyuki Inoue-Mochita; Toshihiro Inoue

doi:10.1016/j.exer.2024.110215

Effect of the IL-6 Trans-signaling Pathway in the Absence or Presence of TGF-β2 on Schlemm's Canal Endothelial Cells

Exp Eye Res. 2024 Dec 20:110215. doi: 10.1016/j.exer.2024.110215. Online ahead of print.

Authors

Mai Urahashi¹, Tomokazu Fujimoto², Miyuki Inoue-Mochita³, Toshihiro Inoue¹

Affiliations

¹ Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
² Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: tomofuji@kumamoto-u.ac.jp.
³ Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.

PMID: 39710100
DOI: 10.1016/j.exer.2024.110215

Abstract

Intraocular pressure (IOP) is regulated through the balance of production and drainage of aqueous humor. The main route of aqueous-humor outflow comprises the trabecular meshwork (TM) and Schlemm's canal (SC). We reported that IL-6 trans-signaling can inhibit TGF-β signaling in TM cells and may affect regulation of IOP. However, the function of IL-6 trans-signaling in SC cells remains unclear. Therefore, we investigated the role of IL-6 trans-signaling in monkey SC cells. Simultaneous treatment with IL-6 and soluble IL-6 receptor (sIL-6R) significantly decreased the trans-endothelial electrical resistance (TER) of SC cells and reduced aqueous-humor outflow resistance. Moreover, activation of IL-6 trans-signaling significantly reduced expression of fibronectin, ZO-1 and claudin-5, and increased that of several matrix metalloproteinases. We also investigated the effect of IL-6 trans-signaling on TGF-β2-induced changes in SC cells. Simultaneous treatment with IL-6 and sIL-6R significantly suppressed the TGF-β2-induced increase in the TER of SC cells but did not affect the activity of the TGF-β2 signaling pathway. By contrast, the TGF-β2-induced increases in the expression of fibronectin and collagen type I were significantly decreased upon simultaneous treatment with IL-6 and sIL-6R. The results show that IL-6 trans-signaling suppressed TGF-β2-induced increase in outflow resistance.

Keywords: Schlemm's canal endothelial cells (SC cells); interleukin 6 (IL-6); soluble interleukin 6 receptor (sIL-6R); transforming growth factor β (TGF-β).