title: Caffeic acid phenethyl ester lessens disease symptoms in an experimental autoimmune uveoretinitis mouse model.
abstract: Experimental autoimmune uveoretinitis (EAU) is an autoimmune disease that models human uveitis. Caffeic acid phenethyl ester (CAPE), a phenolic compound isolated from propolis, possesses anti-inflammatory and immunomodulatory properties. CAPE demonstrates therapeutic potential in several animal disease models through its ability to inhibit NF-κB activity. To evaluate these therapeutic effects in EAU, we administered CAPE in a model of EAU that develops after immunization with interphotoreceptor retinal-binding protein (IRBP) in B10.RIII and C57BL/6 mice. Importantly, we found that CAPE lessened the severity of EAU symptoms in both mouse strains. Notably, treated mice exhibited a decrease in the ocular infiltration of immune cell populations into the retina; reduced TNF-α, IL-6, and IFN-γ serum levels: and inhibited TNF-α mRNA expression in retinal tissues. Although CAPE failed to inhibit IRBP-specific T cell proliferation, it was sufficient to suppress cytokine, chemokine, and IRBP-specific antibody production. In addition, retinal tissues isolated from CAPE-treated EAU mice revealed a decrease in NF-κB p65 and phospho-IκBα. The data identify CAPE as a potential therapeutic agent for autoimmune uveitis that acts by inhibiting cellular infiltration into the retina, reducing the levels of pro-inflammatory cytokines, chemokine, and IRBP-specific antibody and blocking NF-κB pathway activation.
authors: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea; Ocular Neovascular Disease Research Center, Busan Paik Hospital, Busan, Republic of Korea.
authors: Jae-Hyeog
authors: JH
authors: Choi
authors: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea; Ocular Neovascular Disease Research Center, Busan Paik Hospital, Busan, Republic of Korea.
authors: Kug-Hwan
authors: KH
authors: Roh
authors: Ocular Neovascular Disease Research Center, Busan Paik Hospital, Busan, Republic of Korea; Department of Ophthalmology, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.
authors: Hana
authors: H
authors: Oh
authors: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea; Ocular Neovascular Disease Research Center, Busan Paik Hospital, Busan, Republic of Korea.
authors: Sol-Ji
authors: SJ
authors: Park
authors: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea; Ocular Neovascular Disease Research Center, Busan Paik Hospital, Busan, Republic of Korea.
authors: Sung-Min
authors: SM
authors: Ha
authors: Department of Pathology, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.
authors: Mi Seon
authors: MS
authors: Kang
authors: Ocular Neovascular Disease Research Center, Busan Paik Hospital, Busan, Republic of Korea.
authors: Ji-Hyun
authors: JH
authors: Lee
authors: Department of Dermatology, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.
authors: So Young
authors: SY
authors: Jung
authors: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea; Ocular Neovascular Disease Research Center, Busan Paik Hospital, Busan, Republic of Korea.
authors: Hyunkeun
authors: H
authors: Song
authors: Ocular Neovascular Disease Research Center, Busan Paik Hospital, Busan, Republic of Korea; Department of Ophthalmology, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea. Electronic address: oculoplasty@gmail.com.
authors: Jae Wook
authors: JW
authors: Yang
authors: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea; Ocular Neovascular Disease Research Center, Busan Paik Hospital, Busan, Republic of Korea. Electronic address: micpsg@inje.ac.kr.
authors: SaeGwang
authors: S
authors: Park
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002109:Caffeic Acids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D012173:Retinitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014605:Uveitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D002109:Caffeic Acids; D005136:Eye Proteins; D007074:Immunoglobulin G; D007371:Interferon-gamma; D015850:Interleukin-6; D016328:NF-kappa B; D010626:Phenylethyl Alcohol; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D000099214:Retinol-Binding Proteins, Interstitial; C055494:caffeic acid phenethyl ester
keywords: Caffeic acid phenethyl ester; Experimental autoimmune uveoretinitis; Interphotoreceptor retinal-binding protein; Nuclear factor-kappa B; Pro-inflammatory cytokine