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

Angyal, Ágnes and Pénzes, Zsófia and Alimohammadi, Shahrzad and Horváth, Dorottya and Takács, Lili and Vereb, György and Zsebik, Barbara and Bíró, Tamás and Tóth, Kinga Fanni and Lisztes, Erika and Tóth, Balázs István and Oláh, Attila and Szöllősi, Attila (2021) Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (15). ISSN 1661-6596


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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.

Item Type: Article
Additional Information: Funding: This project was supported by Hungarian (NRDIO 125053, 128034, 135938, 134235, 134993, 134725, 134791, EFOP-3.6.3-VEKOP-16-2017-00009, and GINOP-2.3.2-15-2016-00050, GINOP-2.3.3-15-2016-00020) research grants. A.G.S. and B.I.T. were awarded the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. A.G.S. and B.I.T. were supported by the New National Excellence Program of the Ministry for Innovation and Technology (ÚNKP-20-5-DE-100 and ÚNKP-20-5-DE-422, respectively).
Uncontrolled Keywords: Inflammation; ANANDAMIDE; Cornea; endocannabinoid; Toll-like receptor-3 (TLR3);
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
Depositing User: MTMT SWORD
Date Deposited: 28 Sep 2021 13:16
Last Modified: 28 Sep 2021 13:16

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