Interleukin-4 and melatonin ameliorate high glucose and interleukin-1β stimulated inflammatory reaction in human retinal endothelial cells and retinal pigment epithelial cells

Mol Vis. 2014 Jun 28;20:921-8. eCollection 2014.


Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / pathology
  • Down-Regulation / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • Glucose / toxicity*
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology*
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-1beta / toxicity*
  • Interleukin-4 / pharmacology*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Melatonin / pharmacology*
  • Retinal Pigment Epithelium / pathology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Interleukin-1beta
  • Vascular Endothelial Growth Factor A
  • Intercellular Adhesion Molecule-1
  • Interleukin-4
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Glucose
  • Melatonin