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Graefes Arch Clin Exp Ophthalmol. 2017 Sep;255(9):1757-1762. doi: 10.1007/s00417-017-3711-0. Epub 2017 Jun 19.

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

Author information

1
Department of Ophthalmology, University of Turku, Turku, 20521, Finland. olli.arjamaa@utu.fi.
2
Department of Ophthalmology, University of Turku, Turku, 20521, Finland.
3
Department of Ophthalmology, Turku University Hospital, Turku, Finland.
4
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
5
Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland.
6
Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
7
Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, University of Oslo, Oslo, Norway.
8
Department of Ophthalmology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
9
Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.

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.

KEYWORDS:

Human RPE cells; Hypoxia; Inflammation; Interleukins; VEGF

PMID:
28631245
DOI:
10.1007/s00417-017-3711-0
[Indexed for MEDLINE]

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