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Activation of cannabinoid receptor CB2 in ARPE‐19 cells stimulates the release of inflammatory cytokines via activation of the ERK pathway
Author(s) -
HYTTI M,
PIIPPO N,
KORHONEN E,
SALMINEN A,
KAARNIRANTA K,
KAUPPINEN A
Publication year - 2014
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2014.1675.x
Subject(s) - cannabinoid receptor type 2 , cannabinoid receptor , am251 , cannabinoid , mapk/erk pathway , agonist , proinflammatory cytokine , endocannabinoid system , inflammation , cytokine , receptor , pharmacology , microbiology and biotechnology , retinal pigment epithelium , signal transduction , chemistry , viability assay , biology , immunology , retinal , apoptosis , biochemistry
Purpose Endocannabinoid receptors have been suggested to be a possible therapeutical target in age‐related diseases. Particularly CB2, the receptor primarily responsible for the immune modulatory effects of cannabinoids, might be a valuable target in diseases, such as age‐related macular degeneration, where inflammation is known to be a key player. In this study, we have evaluated the effects of CB2 activation on the viability and inflammatory response of retinal pigment epithelial cells. Methods We cultured ARPE‐19 cells until confluent and treated the cells with the selective CB2 agonist JWH‐133. To assess the effect of CB2 activation on oxidatively stressed cells we treated some cells with the lipid peroxidation end product 4‐Hydroxynonenal (HNE) after the JWH‐133 stimulation. The effects of the treatments on cell viability were assessed and inflammatory cytokine expression and signaling protein activation were measured by ELISA. Results Our results show that 10µM JWH‐133 robustly increased the production of interleukin (IL) 6 and IL‐8 in both HNE‐treated and untreated cells. Investigation of the MAPK signaling pathway showed that JWH‐133 at this concentration increased the phosphorylation of ERK1/2. Conclusion Our results show that JWH‐133, a selective agonist of the cannabinoid receptor CB2, stimulates an inflammatory response in ARPE‐19 cells. The release of inflammatory cytokines seems to be mediated by the increased activity of the MAPKinase ERK1/2. Taken together, our results suggest that CB2’s role as a potential therapeutical target in retinal pigment epithelium should be more carefully analyzed in future studies.