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

• Published in: Scientific reports Vol. 7; no. 1; p. 16169
• Main Authors: Hytti, M, Andjelic, S, Josifovska, N, Piippo, N, Korhonen, E, Hawlina, M, Kaarniranta, K, Nevalainen, T J, Petrovski, G, Parkkari, T, Kauppinen, A
• Format: Journal Article
• Language: English
• Published: England 23.11.2017
• Subjects: Cannabinoids - pharmacology; Cell Death - drug effects; Cell Line; Humans; Inflammation - metabolism; Macular Degeneration - metabolism; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Oxidative Stress - drug effects; Receptor, Cannabinoid, CB2 - agonists; Receptor, Cannabinoid, CB2 - metabolism; Retinal Pigment Epithelium - metabolism; Signal Transduction - drug effects
• ISSN: 2045-2322

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 (CB ). Here, we have analysed the effect of CB activation on cellular survival and inflammation in human RPE cells. RPE cells were treated with the selective CB 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 Ca levels, suggesting that RPE cells are capable of responding to a CB 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, CB activation increased, rather than reduced inflammation in RPE cells.