title: Interleukin-4 and melatonin ameliorate high glucose and interleukin-1β stimulated inflammatory reaction in human retinal endothelial cells and retinal pigment epithelial cells.
abstract: OBJECTIVE
  We aimed to evaluate the effects of two immune regulatory factors, interleukin-4 (IL-4) and melatonin, on several inflammatory mediators that are involved in inflammation and angiogenesis in diabetic retinopathy (DR), in high glucose or interleukin-1β (IL-1β) induced primary human retinal endothelial cells (RECs) and human retinal pigment epithelial (RPE) cells.
  
  
  METHODS
  Human RECs and RPE cells were cultured in 30 mM D-glucose or 10 ng/ml IL-1β, with or without the presence of 40 ng/ml IL-4 or 100 μM melatonin. The mRNA and protein levels of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), matrix metalloproteinases 2 (MMP2), and matrix metalloproteinases 9 (MMP9) were measured using real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively.
  
  
  RESULTS
  High glucose and IL-1β induced the expression of VEGF, ICAM-1, MMP2, and MMP9 in human RECs and RPE cells. IL-4 and melatonin downregulated the expression of VEGF, ICAM-1, MMP2, and MMP9 induced by high glucose and IL-1β.
  
  
  CONCLUSIONS
  Our results demonstrated that IL-4 and melatonin inhibited inflammation and angiogenesis triggered by high glucose and IL-1β, which suggests that these immune regulatory factors may be of potential therapeutic value in DR.
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Manyun
authors.initials: M
authors.lastname: Xie
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Andina
authors.initials: A
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xinqian
authors.initials: X
authors.lastname: Hu
authors.affiliation: Aier School of Ophthalmology, Central South University, Changsha, China ; Aier Eye Hospital Group, Changsha, China ; Aier Research Institute of Ophthalmology, Changsha, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Tang
mesh_terms: D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000633:toxicity*; D015847:Interleukin-4 / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D005947:Glucose; D008550:Melatonin