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Resveratrol attenuates CXCL11 expression induced by proinflammatory cytokines in retinal pigment epithelial cells
Affiliation:1. Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, United States;2. Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, United States;3. National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, United States;1. Cornea, Cataract & Refractive Surgery Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India;2. Squint & Neuro-ophthalmology Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India;1. Department of Ophthalmology, Philipps University of Marburg, Marburg, Germany;2. Institute of Medical Biometry and Epidemiology, Philipps University of Marburg, Marburg, Germany;3. SMILE EYES, Marburg, Germany;4. SMILE EYES, Leipzig, Germany;5. SMILE EYES, Muenster, Germany;6. SMILE EYES, Trier, Germany;7. SMILE EYES, Munich, Germany;8. SMILE EYES, Cologne, Germany;9. SMILE EYES, Zentrum Fuer Refraktive Chirurgie, Muenster, Germany;1. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;2. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan;3. School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan;4. Department of Obstetrics and Gynecology, E-Da Hospital, Kaohsiung, Taiwan;5. Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;6. Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;7. Department of Radiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;8. Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan;9. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan;10. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;11. Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan;12. Department of Chemistry and Center for Nanoscience and Nanotechnology, National Sun Yat-sen University, Kaohsiung Taiwan;1. Stem Cell Technology Research Center, Tehran, Iran;2. Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran;3. Department of Clinical Biochemistry, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran;4. Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran;5. Department of Molecular Medicine, School of Medicine, Qazvin University of Medical Science, Qazvin, Iran;1. Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain;2. Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain;3. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain;1. The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea;2. Eyereum Eye Clinic, Seoul, South Korea;3. Emory University School of Medicine, Atlanta, GA, USA
Abstract:Dysfunction of the retinal pigment epithelium (RPE) resulting from chronic inflammation is implicated in the pathogenesis of age-related macular degeneration (AMD). RPE cells adjacent to drusen deposits in the AMD eye are known to contain CXCL11, a chemokine involved in inflammatory cell recruitment. We investigated the CXCL11 production by the human RPE (ARPE-19) cells under inflammatory conditions and tested its response to resveratrol, a naturally occurring anti-inflammatory antioxidant. A proinflammatory cytokine mixture consisting of IFN-γ, IL-1β and TNF-α highly increased CXCL11 mRNA expression and CXCL11 protein secretion by ARPE-19 cells. Resveratrol substantially inhibited the proinflammatory cytokines-induced CXCL11 production while partially blocking nuclear factor-κB activation. This inhibitory action of resveratrol was also observed for the cytokines-induced expression of chemokines CXCL9, CCL2 and CCL5. Our results indicate that resveratrol could potentially attenuate RPE inflammatory response implicated in the pathogenesis of AMD.
Keywords:Resveratrol  Retinal pigment epithelium  Age-related macular degeneration  CXCL11  Nuclear factor-kappa B
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