CB 2 receptor activation causes an ERK1/2-dependent inflammatory response in human RPE cells
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 pigm...
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Published in | Scientific reports Vol. 7; no. 1; p. 16169 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
23.11.2017
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Subjects | |
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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 (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. |
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AbstractList | 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. |
Author | Kaarniranta, K Hawlina, M Nevalainen, T J Piippo, N Parkkari, T Andjelic, S Josifovska, N Korhonen, E Hytti, M Kauppinen, A Petrovski, G |
Author_xml | – sequence: 1 givenname: M surname: Hytti fullname: Hytti, M email: maria.hytti@uef.fi, maria.hytti@uef.fi organization: Department of Ophthalmology, School of Medicine, University of Eastern Finland, Kuopio, Finland. maria.hytti@uef.fi – sequence: 2 givenname: S surname: Andjelic fullname: Andjelic, S organization: Eye Hospital, University Medical Centre, Ljubljana, Slovenia – sequence: 3 givenname: N surname: Josifovska fullname: Josifovska, N organization: Stem Cells and Eye Research Laboratory, Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary – sequence: 4 givenname: N surname: Piippo fullname: Piippo, N organization: Department of Ophthalmology, School of Medicine, University of Eastern Finland, Kuopio, Finland – sequence: 5 givenname: E surname: Korhonen fullname: Korhonen, E organization: Department of Ophthalmology, School of Medicine, University of Eastern Finland, Kuopio, Finland – sequence: 6 givenname: M surname: Hawlina fullname: Hawlina, M organization: Eye Hospital, University Medical Centre, Ljubljana, Slovenia – sequence: 7 givenname: K surname: Kaarniranta fullname: Kaarniranta, K organization: Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland – sequence: 8 givenname: T J surname: Nevalainen fullname: Nevalainen, T J organization: School of Pharmacy, University of Eastern Finland, Kuopio, Finland – sequence: 9 givenname: G surname: Petrovski fullname: Petrovski, G organization: Centre of Eye Research, Department of Ophthalmology and the Norwegian Center for Stem Cell Research, Oslo University Hospital, University of Oslo, Oslo, Norway – sequence: 10 givenname: T surname: Parkkari fullname: Parkkari, T organization: School of Pharmacy, University of Eastern Finland, Kuopio, Finland – sequence: 11 givenname: A orcidid: 0000-0001-8254-0200 surname: Kauppinen fullname: Kauppinen, A organization: School of Pharmacy, University of Eastern Finland, Kuopio, Finland |
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SubjectTerms | 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 |
Title | CB 2 receptor activation causes an ERK1/2-dependent inflammatory response in human RPE cells |
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