{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:50:19Z","timestamp":1776210619466,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["125053"],"award-info":[{"award-number":["125053"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["128034"],"award-info":[{"award-number":["128034"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["135938"],"award-info":[{"award-number":["135938"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["134235"],"award-info":[{"award-number":["134235"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["134993"],"award-info":[{"award-number":["134993"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["134725"],"award-info":[{"award-number":["134725"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["134791"],"award-info":[{"award-number":["134791"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005881","name":"Emberi Eroforr\u00e1sok Miniszt\u00e9riuma","doi-asserted-by":"publisher","award":["EFOP-3.6.3-VEKOP-16-2017-00009"],"award-info":[{"award-number":["EFOP-3.6.3-VEKOP-16-2017-00009"]}],"id":[{"id":"10.13039\/501100005881","id-type":"DOI","asserted-by":"publisher"}]},{"name":"P\u00e9nz\u00fcgyi Miniszt\u00e9rium","award":["GINOP-2.3.2-15-2016-00050"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00050"]}]},{"name":"P\u00e9nz\u00fcgyi Miniszt\u00e9rium","award":["GINOP-2.3.3-15-2016-00020"],"award-info":[{"award-number":["GINOP-2.3.3-15-2016-00020"]}]},{"name":"J\u00e1nos B\u00f3lyai Research Scholarship","award":["BO\/00491\/18"],"award-info":[{"award-number":["BO\/00491\/18"]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology","award":["\u00daNKP-20-5-DE-100"],"award-info":[{"award-number":["\u00daNKP-20-5-DE-100"]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology","award":["\u00daNKP-20-5-DE-422"],"award-info":[{"award-number":["\u00daNKP-20-5-DE-422"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03bcM, 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.<\/jats:p>","DOI":"10.3390\/ijms22157776","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T11:53:23Z","timestamp":1626868403000},"page":"7776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"\u00c1gnes","family":"Angyal","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zs\u00f3fia","family":"P\u00e9nzes","sequence":"additional","affiliation":[{"name":"Doctoral School of Molecular Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Department of Immunology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4867-9337","authenticated-orcid":false,"given":"Shahrzad","family":"Alimohammadi","sequence":"additional","affiliation":[{"name":"Doctoral School of Molecular Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Department of Immunology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorottya","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Doctoral School of Molecular Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Department of Immunology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Tak\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-3265","authenticated-orcid":false,"given":"Gy\u00f6rgy","family":"Vereb","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"MTA-DE Cell Biology and Signaling Research Group, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Faculty of Pharmacy, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Zsebik","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"MTA-DE Cell Biology and Signaling Research Group, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"B\u00edr\u00f3","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Monasterium Laboratory Skin & Hair Research Solutions, Mendelstra\u00dfe 17, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5184-8082","authenticated-orcid":false,"given":"Kinga Fanni","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Department of Immunology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Lisztes","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-4333","authenticated-orcid":false,"given":"Bal\u00e1zs Istv\u00e1n","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4122-5639","authenticated-orcid":false,"given":"Attila","family":"Ol\u00e1h","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6046-8236","authenticated-orcid":false,"given":"Attila G\u00e1bor","family":"Sz\u00f6ll\u0151si","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.4103\/jovr.jovr_114_17","article-title":"Invisible Shield: Review of the Corneal Epithelium as a Barrier to UV Radiation, Pathogens, and Other Environmental Stimuli","volume":"12","author":"Bashir","year":"2017","journal-title":"J. Ophthalmic Vis. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000187623","article-title":"Role of Cysteine in Corneal Wound Healing after Photorefractive Keratectomy","volume":"41","author":"Meduri","year":"2009","journal-title":"Ophthalmic Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2147\/OPTH.S16866","article-title":"Effect of Basic Fibroblast Growth Factor and Cytochrome c Peroxidase Combination in Transgenic Mice Corneal + Epithelial Healing Process after Excimer Laser Photoablation","volume":"5","author":"Scalinci","year":"2011","journal-title":"Clin. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"424","DOI":"10.4103\/0301-4738.119420","article-title":"Effect of the Combination of Basic Fibroblast Growth Factor and Cysteine on Corneal Epithelial Healing after Photorefractive Keratectomy in Patients Affected by Myopia","volume":"62","author":"Meduri","year":"2014","journal-title":"Indian J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.brainres.2006.02.035","article-title":"Peripheral and Central Distribution of TRPV1, Substance P and CGRP of Rat Corneal Neurons","volume":"1085","author":"Murata","year":"2006","journal-title":"Brain Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/jcp.21141","article-title":"Transient Receptor Potential Vanilloid 1 Activation Induces Inflammatory Cytokine Release in Corneal Epithelium through MAPK Signaling","volume":"213","author":"Zhang","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0896-6273(00)80564-4","article-title":"The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli","volume":"21","author":"Tominaga","year":"1998","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.freeradbiomed.2019.10.415","article-title":"Transient Receptor Potential (TRP) Channels: Biosensors for Redox Environmental Stimuli and Cellular Status","volume":"146","author":"Sakaguchi","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1016\/j.ajpath.2011.02.043","article-title":"TRPV1 Involvement in Inflammatory Tissue Fibrosis in Mice","volume":"178","author":"Okada","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1124\/mol.56.3.581","article-title":"The Cloned Rat Vanilloid Receptor VR1 Mediates Both R-Type Binding and C-Type Calcium Response in Dorsal Root Ganglion Neurons","volume":"56","author":"Szallasi","year":"1999","journal-title":"Mol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.pain.2010.03.024","article-title":"Prolonged Analgesic Response of Cornea to Topical Resiniferatoxin, a Potent TRPV1 Agonist","volume":"149","author":"Bates","year":"2010","journal-title":"Pain"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bukiya, A.N. (2019). Pharmacology of Medical Cannabis. Recent Advances in Cannabinoid Physiology and Pathology, Springer International Publishing.","DOI":"10.1007\/978-3-030-21737-2"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"T\u00f3th, K.F., \u00c1d\u00e1m, D., B\u00edr\u00f3, T., and Ol\u00e1h, A. (2019). Cannabinoid Signaling in the Skin: Therapeutic Potential of the \u201cC(Ut)Annabinoid\u201d System. Molecules, 24.","DOI":"10.3390\/molecules24050918"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/BF01863673","article-title":"Pharmakologische Wertbestimmung von orientalischem Haschisch und Herba cannabis indicae","volume":"129","author":"Gayer","year":"1928","journal-title":"Naunyn Schmiedebergs Archiv f\u00fcr Experimentelle Pathologie und Pharmakologie"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/BF00402387","article-title":"Structure Activity Relationship of Four Tetrahydrocannabinols and the Pharmacological Activity of Five Semi-Purified Extracts of Cannabis Sativa","volume":"18","author":"Carlini","year":"1970","journal-title":"Psychopharmacologia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1476-5381.1974.tb08576.x","article-title":"Effects of Marihuana in Laboratory Animals and in Man","volume":"50","author":"Carlini","year":"1974","journal-title":"Br. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S0304-3959(02)00271-3","article-title":"Topical Cannabinoid Agonist, WIN55,212-2, Reduces Cornea-Evoked Trigeminal Brainstem Activity in the Rat","volume":"99","author":"Bereiter","year":"2002","journal-title":"Pain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.exer.2010.06.022","article-title":"Epidermal Growth Factor Receptor Transactivation by the Cannabinoid Receptor (CB1) and Transient Receptor Potential Vanilloid 1 (TRPV1) Induces Differential Responses in Corneal Epithelial Cells","volume":"91","author":"Yang","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/jid.2010.421","article-title":"Endocannabinoids Modulate Human Epidermal Keratinocyte Proliferation and Survival via the Sequential Engagement of Cannabinoid Receptor-1 and Transient Receptor Potential Vanilloid-1","volume":"131","author":"Dobrosi","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.bbrc.2005.03.095","article-title":"Finding of Endocannabinoids in Human Eye Tissues: Implications for Glaucoma","volume":"330","author":"Chen","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1054\/plef.2001.0356","article-title":"Biosynthesis and Degradation of Anandamide and 2-Arachidonoylglycerol and Their Possible Physiological Significance","volume":"66","author":"Sugiura","year":"2002","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1365-2567.2005.02258.x","article-title":"Toll-like Receptor 3 Agonist Poly(I:C)-Induced Antiviral Response in Human Corneal Epithelial Cells","volume":"117","author":"Kumar","year":"2006","journal-title":"Immunology"},{"key":"ref_23","first-page":"2483","article-title":"Ultraviolet Irradiation Induces the Production of Multiple Cytokines by Human Corneal Cells","volume":"38","author":"Kennedy","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/php.12686","article-title":"Damaging Effects of Ultraviolet Radiation on the Cornea","volume":"93","author":"Delic","year":"2017","journal-title":"Photochem. Photobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.exer.2019.03.011","article-title":"Cannabinoid CB2R Receptors Are Upregulated with Corneal Injury and Regulate the Course of Corneal Wound Healing","volume":"182","author":"Murataeva","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.brainresbull.2009.05.019","article-title":"Corneal Transparency: Genesis, Maintenance and Dysfunction","volume":"81","author":"Qazi","year":"2010","journal-title":"Brain Res. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3109\/08830185.2012.749400","article-title":"Host Defense at the Ocular Surface","volume":"32","author":"Pearlman","year":"2013","journal-title":"Int. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1167\/iovs.17-23279","article-title":"Corneal Epithelial Cells Exhibit Myeloid Characteristics and Present Antigen via MHC Class II","volume":"59","author":"Royer","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1080\/09273948.2016.1231330","article-title":"TRPV1 Antagonist Suppresses Allergic Conjunctivitis in a Murine Model","volume":"26","author":"Kwon","year":"2018","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Garami, A., Pakai, E., McDonald, H.A., Reilly, R.M., Gomtsyan, A., Corrigan, J.J., Pinter, E., Zhu, D.X.D., Lehto, S.G., and Gavva, N.R. (2018). TRPV1 Antagonists That Cause Hypothermia, Instead of Hyperthermia, in Rodents: Compounds\u2019 Pharmacological Profiles, in Vivo Targets, Thermoeffectors Recruited and Implications for Drug Development. Acta Physiol., 223.","DOI":"10.1111\/apha.13038"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/med.21427","article-title":"Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists","volume":"37","author":"Baraldi","year":"2017","journal-title":"Med. Res. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.plefa.2006.08.002","article-title":"Changes in Endocannabinoid and Palmitoylethanolamide Levels in Eye Tissues of Patients with Diabetic Retinopathy and Age-Related Macular Degeneration","volume":"75","author":"Matias","year":"2006","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/sj.bjp.0705666","article-title":"The Endocannabinoid System: A General View and Latest Additions","volume":"141","author":"Petrocellis","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.disamonth.2014.03.003","article-title":"Herpes Simplex Keratitis","volume":"60","author":"Hill","year":"2014","journal-title":"Dis. Mon."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1089\/ham.2015.0109","article-title":"Ultraviolet Keratitis: From the Pathophysiological Basis to Prevention and Clinical Management","volume":"16","author":"Willmann","year":"2015","journal-title":"High. Alt. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0304-3940(02)01221-1","article-title":"Concentration-Dependent Dual Effect of Anandamide on Sensory Neuropeptide Release from Isolated Rat Tracheae","volume":"336","author":"Helyes","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Thapa, D., Cairns, E.A., Szczesniak, A.-M., Kulkarni, P.M., Straiker, A.J., Thakur, G.A., and Kelly, M.E.M. (2020). Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation. Molecules, 25.","DOI":"10.3390\/molecules25020417"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1038\/sj.bjp.0707460","article-title":"The Orphan Receptor GPR55 Is a Novel Cannabinoid Receptor","volume":"152","author":"Ryberg","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1111\/j.1476-5381.2011.01497.x","article-title":"\u0394(9) -Tetrahydrocannabinol and N-Arachidonyl Glycine Are Full Agonists at GPR18 Receptors and Induce Migration in Human Endometrial HEC-1B Cells","volume":"165","author":"McHugh","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7033","DOI":"10.1093\/emboj\/20.24.7033","article-title":"Direct Inhibition of T-Type Calcium Channels by the Endogenous Cannabinoid Anandamide","volume":"20","author":"Chemin","year":"2001","journal-title":"EMBO J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/emboj\/20.1.47","article-title":"The Endocannabinoid Anandamide Is a Direct and Selective Blocker of the Background K(+) Channel TASK-1","volume":"20","author":"Maingret","year":"2001","journal-title":"EMBO J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1016\/j.yexcr.2007.01.008","article-title":"Regulation of Transient Receptor Potential Channels of Melastatin Type 8 (TRPM8): Effect of CAMP, Cannabinoid CB(1) Receptors and Endovanilloids","volume":"313","author":"Starowicz","year":"2007","journal-title":"Exp. Cell Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/0028-3908(96)00130-X","article-title":"Anandamide, an Endogenous Cannabinoid, Inhibits Shaker-Related Voltage-Gated K+ Channels","volume":"35","author":"Poling","year":"1996","journal-title":"Neuropharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1111\/bph.12136","article-title":"A GPR18-Based Signalling System Regulates IOP in Murine Eye","volume":"169","author":"Caldwell","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1097\/ICO.0000000000001934","article-title":"Evidence for a GPR18 Role in Chemotaxis, Proliferation, and the Course of Wound Closure in the Cornea","volume":"38","author":"Murataeva","year":"2019","journal-title":"Cornea"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cellsig.2015.12.005","article-title":"3-Iodothyronamine Increases Transient Receptor Potential Melastatin Channel 8 (TRPM8) Activity in Immortalized Human Corneal Epithelial Cells","volume":"28","author":"Lucius","year":"2016","journal-title":"Cell. Signal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S212","DOI":"10.1016\/j.jid.2016.06.323","article-title":"303 Establishment and Optimization of Pro-Inflammatory Model Systems in Human Keratinocytes","volume":"136","author":"Angyal","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/7776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:32:43Z","timestamp":1760164363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/7776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,21]]},"references-count":48,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22157776"],"URL":"https:\/\/doi.org\/10.3390\/ijms22157776","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,21]]}}}