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Sci Rep. 2017 Nov 23;7(1):16169. doi: 10.1038/s41598-017-16524-w.

CB2 receptor activation causes an ERK1/2-dependent inflammatory response in human RPE cells.

Author information

1
School of Pharmacy, University of Eastern Finland, Kuopio, Finland. maria.hytti@uef.fi.
2
Department of Ophthalmology, School of Medicine, University of Eastern Finland, Kuopio, Finland. maria.hytti@uef.fi.
3
Eye Hospital, University Medical Centre, Ljubljana, Slovenia.
4
Stem Cells and Eye Research Laboratory, Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
5
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
6
Department of Ophthalmology, School of Medicine, University of Eastern Finland, Kuopio, Finland.
7
Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
8
Centre of Eye Research, Department of Ophthalmology and the Norwegian Center for Stem Cell Research, Oslo University Hospital, University of Oslo, Oslo, Norway.

Abstract

A chronic low-level inflammation contributes to the pathogenesis of age-related macular degeneration (AMD), the most common cause of blindness in the elderly in Western countries. The loss of central vision results from attenuated maintenance of photoreceptors due to the degeneration of retinal pigment epithelium (RPE) cells beneath the photoreceptor layer. It has been proposed that pathologic inflammation initiated in RPE cells could be regulated by the activation of type 2 cannabinoid receptors (CB2). Here, we have analysed the effect of CB2 activation on cellular survival and inflammation in human RPE cells. RPE cells were treated with the selective CB2 agonist JWH-133 in the presence or absence of the oxidative stressor 4-hydroxynonenal. Thereafter, cellular viability as well as the release of pro-inflammatory cytokines and potential underlying signalling pathways were analysed. Our results show that JWH-133 led to increased intracellular Ca2+ levels, suggesting that RPE cells are capable of responding to a CB2 agonist. JWH-133 could not prevent oxidative stress-induced cell death. Instead, 10 µM JWH-133 increased cell death and the release of proinflammatory cytokines in an ERK1/2-dependent manner. In contrast to previous findings, CB2 activation increased, rather than reduced inflammation in RPE cells.

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