机构:[1]The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.[2]Chongqing Key Laboratory of Ophthalmology, Chongqing, China.[3]Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.[4]The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.重庆医科大学附属第一医院[5]The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.[6]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.研究所眼科研究所首都医科大学附属北京同仁医院首都医科大学附属同仁医院
Apigenin is a natural small molecule compound widely present in various vegetables and fruits. Recently, Apigenin was reported to inhibit lipopolysaccharide (LPS)-simulated microglial proinflammatory activation. Considering the important role of microglia in retinal disorders, we wonder whether Apigenin could exert a therapeutic effect on experimental autoimmune uveitis (EAU) through reprogramming retinal microglia to a beneficial subtype.EAU was induced in C57BL/6J mice by immunization with interphotoreceptor retinoid-binding protein (IRBP)651-670, followed by intraperitoneal administration of Apigenin. Disease severity was assessed based on clinical and pathological scores. In vivo, Western blotting was used to quantify protein levels of classical inflammatory factors, microglial M1/M2 markers and the tight junction protein of the blood-retinal-barrier (BRB). Immunofluorescence was used to determine the Apigenin's efficacy on microglial phenotype. In vitro, Apigenin was added in LPS and IFN-γ stimulated human microglial cell line. Western blotting and Transwell assays were used to analyze the phenotype of microglia.In vivo, we found that Apigenin significantly reduced the clinical and pathological scores of EAU. The protein levels of inflammatory cytokines were significantly decreased in retina, and BRB disruption was ameliorated after Apigenin treatment. Meanwhile, Apigenin inhibited microglia M1 transition in EAU mice retina. In vitro functional studies showed that Apigenin decreased LPS and IFN-γ-induced microglial inflammatory factor production and M1-activation via the TLR4/MyD88 pathway.Apigenin can ameliorate retinal inflammation in IRBP induced autoimmune uveitis through inhibiting microglia M1 pro-inflammatory polarization via TLR4/MyD88 pathway.
基金:
National Natural Science Foundation Project
of China (82070951, 82271078), the National Key Clinical
Specialties Construction Program of China, Chongqing
Branch of the National Clinical Research Center for Ocular
Diseases, Chongqing Key Laboratory of Ophthalmology (CSTC,
2008CA5003), and the Program for Youth Innovation in Future
Medicine, Chongqing Medical University (w0047).
第一作者机构:[1]The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.[2]Chongqing Key Laboratory of Ophthalmology, Chongqing, China.[3]Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.
共同第一作者:
通讯作者:
通讯机构:[1]The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.[2]Chongqing Key Laboratory of Ophthalmology, Chongqing, China.[3]Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.[4]The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.[5]The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.[6]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.[*1]Shengping Hou, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China[*2]Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China[*3]Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Anhui 230601, China
推荐引用方式(GB/T 7714):
Shu Nan,Zhang Zhi,Wang Xiaotang,et al.Apigenin Alleviates Autoimmune Uveitis by Inhibiting Microglia M1 Pro-Inflammatory Polarization[J].INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE.2023,64(5):doi:10.1167/iovs.64.5.21.
APA:
Shu Nan,Zhang Zhi,Wang Xiaotang,Li Ruonan,Li Wanqian...&Hou Shengping.(2023).Apigenin Alleviates Autoimmune Uveitis by Inhibiting Microglia M1 Pro-Inflammatory Polarization.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,64,(5)
MLA:
Shu Nan,et al."Apigenin Alleviates Autoimmune Uveitis by Inhibiting Microglia M1 Pro-Inflammatory Polarization".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 64..5(2023)