title: Reverse Translational Study of Fenofibrate's Observed Effects in Diabetes-Associated Retinopathy.
abstract: Clinical trials suggest that fenofibrate reduces the progression of retinopathies in patients with type 2 diabetes. Furthermore, patients with retinopathies have elevated levels of inflammatory chemokines and dysfunctional retinal angiogenesis. Therefore, we investigated the effects of fenofibrate on the production of inflammatory chemokines and genes associated with angiogenesis. Retinal pigment epithelial cells (RPECs) were cultured with IL-1β and fenofibrate ranging from 1-50 μM. ENA-78, IL-8, and RANTES were measured in cell culture by ELISA. ENA-78, ABCA1, and ABCG1 gene expression were tested by RT-PCR. IL-1β significantly induced the production of ENA-78, IL-8, and RANTES. Fenofibrate at concentrations of 25-50 uM blunted the IL-1β induced production of ENA-78 (p < 0.05) with no significant effects on RANTES and IL-8. Fenofibrate also reduced the expression of the ENA-78 gene as well as ABCA1 and ABCG1, which are genes involved in angiogenesis. Fenofibrate decreases ENA-78 production and ABCA1/ABCG1 gene expression in RPECs.
authors.affiliation: Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, Arkansas, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Farris
authors.affiliation: Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, Arkansas, USA.
authors.forename: E T
authors.initials: ET
authors.lastname: Price
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D055213:Retinal Pigment Epithelium / Q000166:cytology
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D015415:Biomarkers; C483024:CCL5 protein, human; C486263:CXCL5 protein, human; C508606:CXCL8 protein, human; D018946:Chemokine CCL5; D054365:Chemokine CXCL5; D000960:Hypolipidemic Agents; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; D011345:Fenofibrate