Hypoxia and inflammation in the release of VEGF and interleukins from human retinal pigment epithelial cells

Olli Arjamaa, Vesa Aaltonen, Niina Piippo, T. Csont, G. Petrovski, Kai Kaarniranta, Anu Kauppinen

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: Retinal diseases are closely associated with both decreased oxygenation and increased inflammation. It is not known if hypoxia-induced vascular endothelial growth factor (VEGF) expression in the retina itself evokes inflammation, or whether inflammation is a prerequisite for the development of neovascularization. Methods: Human ARPE-19 cell line and primary human retinal pigment epithelium (RPE) cells were used. ARPE-19 cells were kept either under normoxic (24 h or 48 h) or hypoxic conditions (1% O2, 24 h). Part of the cells were re-oxygenated (24 h). Some ARPE-19 cells were additionally pre-treated with bacterial lipopolysaccharide (LPS). The levels of IL-6, IL-8, IL-1β, and IL-18 were determined from medium samples by an enzyme-linked immunosorbent assay (ELISA) method. Primary human RPE cells were exposed to hypoxia for 24 h, and the subsequent release of IL-6 and IL-8 was measured with ELISA. VEGF secretion from ARPE-19 cells was determined up to 24 h. Results: Hypoxia induced significant (P < 0.01) increases in the levels of both IL-6 and IL-8 in ARPE-19 cells, and LPS pre-treatment further enhanced these responses. Hypoxia exposure did not affect the IL-1β or IL-18 release irrespective of LPS pre-treatment. If primary RPE cells were incubated for 4 h in hypoxic conditions, IL-6 and IL-8 concentrations were increased by 7 and 8-fold respectively. Hypoxia increased the VEGF secretion from ARPE-19 cells in a similar manner with or without pre-treatment with LPS. Conclusions: Hypoxia causes an inflammatory reaction in RPE cells that is potentiated by pre-treatment with the Toll-like receptor-activating agent, LPS. The secretion of VEGF from these cells is regulated directly by hypoxia and is not mediated by inflammation.

Original languageEnglish
Pages (from-to)1757-1762
Number of pages6
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume255
Issue number9
DOIs
Publication statusPublished - Sep 1 2017

Keywords

  • Human RPE cells
  • Hypoxia
  • Inflammation
  • Interleukins
  • VEGF

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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