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Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells

Photodamage-induced and viral keratitis could benefit from treatment with novel nonsteroid anti-inflammatory agents. Therefore, we determined whether human corneal epithelial cells (HCECs) express members of the endocannabinoid system (ECS), and examined how the endocannabinoid anandamide (AEA, N-ar...

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Autores principales: Angyal, Ágnes, Pénzes, Zsófia, Alimohammadi, Shahrzad, Horváth, Dorottya, Takács, Lili, Vereb, György, Zsebik, Barbara, Bíró, Tamás, Tóth, Kinga Fanni, Lisztes, Erika, Tóth, Balázs István, Oláh, Attila, Szöllősi, Attila Gábor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346008/
https://www.ncbi.nlm.nih.gov/pubmed/34360541
http://dx.doi.org/10.3390/ijms22157776
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author Angyal, Ágnes
Pénzes, Zsófia
Alimohammadi, Shahrzad
Horváth, Dorottya
Takács, Lili
Vereb, György
Zsebik, Barbara
Bíró, Tamás
Tóth, Kinga Fanni
Lisztes, Erika
Tóth, Balázs István
Oláh, Attila
Szöllősi, Attila Gábor
author_facet Angyal, Ágnes
Pénzes, Zsófia
Alimohammadi, Shahrzad
Horváth, Dorottya
Takács, Lili
Vereb, György
Zsebik, Barbara
Bíró, Tamás
Tóth, Kinga Fanni
Lisztes, Erika
Tóth, Balázs István
Oláh, Attila
Szöllősi, Attila Gábor
author_sort Angyal, Ágnes
collection PubMed
description Photodamage-induced and viral keratitis could benefit from treatment with novel nonsteroid anti-inflammatory agents. Therefore, we determined whether human corneal epithelial cells (HCECs) express members of the endocannabinoid system (ECS), and examined how the endocannabinoid anandamide (AEA, N-arachidonoyl ethanolamine) influences the Toll-like receptor 3 (TLR3) agonism- or UVB irradiation-induced inflammatory response of these cells. Other than confirming the presence of cannabinoid receptors, we show that endocannabinoid synthesizing and catabolizing enzymes are also expressed in HCECs in vitro, as well as in the epithelial layer of the human cornea in situ, proving that they are one possible source of endocannabinoids. p(I:C) and UVB irradiation was effective in promoting the transcription and secretion of inflammatory cytokines. Surprisingly, when applied alone in 100 nM and 10 μM, AEA also resulted in increased pro-inflammatory cytokine production. Importantly, AEA further increased levels of these cytokines in the UVB model, whereas its lower concentration partially prevented the transcriptional effect of p(I:C), while not decreasing the p(I:C)-induced cytokine release. HCECs express the enzymatic machinery required to produce endocannabinoids both in vitro and in situ. Moreover, our data show that, despite earlier reports about the anti-inflammatory potential of AEA in murine cornea, its effects on the immune phenotype of human corneal epithelium may be more complex and context dependent.
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spelling pubmed-83460082021-08-07 Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells Angyal, Ágnes Pénzes, Zsófia Alimohammadi, Shahrzad Horváth, Dorottya Takács, Lili Vereb, György Zsebik, Barbara Bíró, Tamás Tóth, Kinga Fanni Lisztes, Erika Tóth, Balázs István Oláh, Attila Szöllősi, Attila Gábor Int J Mol Sci Article Photodamage-induced and viral keratitis could benefit from treatment with novel nonsteroid anti-inflammatory agents. Therefore, we determined whether human corneal epithelial cells (HCECs) express members of the endocannabinoid system (ECS), and examined how the endocannabinoid anandamide (AEA, N-arachidonoyl ethanolamine) influences the Toll-like receptor 3 (TLR3) agonism- or UVB irradiation-induced inflammatory response of these cells. Other than confirming the presence of cannabinoid receptors, we show that endocannabinoid synthesizing and catabolizing enzymes are also expressed in HCECs in vitro, as well as in the epithelial layer of the human cornea in situ, proving that they are one possible source of endocannabinoids. p(I:C) and UVB irradiation was effective in promoting the transcription and secretion of inflammatory cytokines. Surprisingly, when applied alone in 100 nM and 10 μM, AEA also resulted in increased pro-inflammatory cytokine production. Importantly, AEA further increased levels of these cytokines in the UVB model, whereas its lower concentration partially prevented the transcriptional effect of p(I:C), while not decreasing the p(I:C)-induced cytokine release. HCECs express the enzymatic machinery required to produce endocannabinoids both in vitro and in situ. Moreover, our data show that, despite earlier reports about the anti-inflammatory potential of AEA in murine cornea, its effects on the immune phenotype of human corneal epithelium may be more complex and context dependent. MDPI 2021-07-21 /pmc/articles/PMC8346008/ /pubmed/34360541 http://dx.doi.org/10.3390/ijms22157776 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Angyal, Ágnes
Pénzes, Zsófia
Alimohammadi, Shahrzad
Horváth, Dorottya
Takács, Lili
Vereb, György
Zsebik, Barbara
Bíró, Tamás
Tóth, Kinga Fanni
Lisztes, Erika
Tóth, Balázs István
Oláh, Attila
Szöllősi, Attila Gábor
Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells
title Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells
title_full Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells
title_fullStr Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells
title_full_unstemmed Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells
title_short Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells
title_sort anandamide concentration-dependently modulates toll-like receptor 3 agonism or uvb-induced inflammatory response of human corneal epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346008/
https://www.ncbi.nlm.nih.gov/pubmed/34360541
http://dx.doi.org/10.3390/ijms22157776
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