Human retinal endothelial cells express functional interleukin-6 receptor

Lisia Barros Ferreira, Liam M. Ashander, Binoy Appukuttan, Yuefang Ma, Keryn A. Williams, Giles Best, Justine R. Smith

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
29 Downloads (Pure)

Abstract

Background: Interleukin (IL)-6 is an inflammatory cytokine present in the eye during non-infectious uveitis, where it contributes to the progression of inflammation. There are two major IL-6 signaling pathways: classic signaling and trans-signaling. Classic signaling requires cellular expression of the IL-6 receptor (IL-6R), which exists in membrane-bound (mIL-6R) and soluble (sIL-6R) forms. Prevailing dogma is that vascular endothelial cells do not produce IL-6R, relying on trans-signaling during inflammation. However, the literature is inconsistent, including with respect to human retinal endothelial cells. 

Findings: We examined IL-6R transcript and protein expression in multiple primary human retinal endothelial cell isolates, and assessed the effect of IL-6 on the transcellular electrical resistance of monolayers. Using reverse transcription-polymerase chain reaction, IL-6R, mIL-6R and sIL-6R transcripts were amplified in 6 primary human retinal endothelial isolates. Flow cytometry on 5 primary human retinal endothelial cell isolates under non-permeabilizing conditions and following permeabilization demonstrated intracellular stores of IL-6R and the presence of mIL-6R. When measured in real-time, transcellular electrical resistance of an expanded human retinal endothelial cell isolate, also shown to express IL-6R, decreased significantly on treatment with recombinant IL-6 in comparison to non-treated cells across 5 independent experiments. 

Conclusions: Our findings indicate that human retinal endothelial cells produce IL-6R transcript and functional IL-6R protein. The potential for classic signaling in human retinal endothelial cells has implications for the development of therapeutics targeted against IL-6-mediated pathology in non-infectious uveitis.

Original languageEnglish
Article number21
Number of pages8
JournalJournal of Ophthalmic Inflammation and Infection
Volume13
DOIs
Publication statusPublished - 25 Apr 2023

Keywords

  • Endothelial cell
  • Human
  • Interleukin-6
  • Receptor
  • Retina
  • Uveitis

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