title: Exendin-4 and GLP-1 decreases induced expression of ICAM-1, VCAM-1 and RAGE in human retinal pigment epithelial cells.
abstract: BACKGROUND
  Advanced glycation end products (AGEs) take part in the development of diabetic retinopathy. Hyperglycemia triggers an inflammatory response in the retina. These mechanisms may lead to an enhanced expression of adhesion molecules (ICAM-1 and VCAM-1) in human retinal pigment epithelium (HRPE). Glucagon-like peptide 1 (GLP-1) functions as an incretin hormone with antidiabetogenic properties. GLP-1 also possesses vasoprotective properties.
  
  
  METHODS
  The aim of our study was to evaluate the influence of glycated albumin (GlyAlb; 100; 500 and 1000 mg/l) and pro-inflammatory cytokine, TNF-α (2.5 and 10 ng/ml), on expression of RAGE, ICAM-1 and VCAM-1 and to evaluate the influence of GLP-1 (100 nM) and its analogue, exendin-4 (10 nM), on the expression of RAGE, ICAM-1 and VCAM-1 in stimulated HRPE.
  
  
  RESULTS
  TNF-α increased RAGE expression in HRPE cells. The addition of GlyAlb (500 and 1000 mg/l) resulted in a decrease of RAGE expression. Both TNF-α and GlyAlb increased the secretion of both adhesion molecules. In cells co-treated with GLP-1 or exendin-4 both incretins decreased RAGE expression in TNF-α treated cells, and in GlyAlb group. The ICAM-1 expression was lowered by exendin-4 and GLP-1 in cells stimulated by TNF-α and GlyAlb. The similar results were obtained for VCAM-1. All observed alterations were statistically significant.
  
  
  CONCLUSIONS
  The obtained results indicate that both GLP-1 and exendin-4 by decreasing the expression of RAGE in HRPE can make these cells more resistant to circulating AGEs, and decreased expression of circulating VCAM-1 and ICAM-1, can be the result of anti-inflammatory properties of incretins and decreased expression of RAGE.
authors.affiliation: Department of Ophthalmology, Medical University of Silesia, Ceglana 35, PL 40-952 Katowice, Poland. ksiem@mp.pl.
authors.forename: Mariola
authors.initials: M
authors.lastname: Dorecka
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Siemianowicz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Francuz
authors.forename: Wojciech
authors.initials: W
authors.lastname: Garczorz
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chyra
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Klych
authors.forename: Wanda
authors.initials: W
authors.lastname: Romaniuk
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D017127:Glycation End Products, Advanced; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D012709:Serum Albumin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology*; D000093423:Glycated Serum Albumin
chemical_list: D017127:Glycation End Products, Advanced; D010455:Peptides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D014688:Venoms; D018799:Intercellular Adhesion Molecule-1; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D000093423:Glycated Serum Albumin