trans-resveratrol inhibits hyperglycemia-induced inflammation and connexin downregulation in retinal pigment epithelial cells.
The purpose of this study was to determine the inhibitory activity of trans-resveratrol against hyperglycemia-induced inflammation and degradation of gap junction intercellular communication in retinal pigment epithelial cells. Retinal (ARPE-19) cells were incubated with 5.5 mM glucose, 5.5 mM glucose and 10 microM resveratrol, 33 mM glucose, or 33 mM glucose and 0-10 microM trans-resveratrol at 37 degrees C and 5% CO(2) for 9 days. Cell viability was determined by the crystal violet assay. The levels of low-grade inflammation biomarkers interleukin-6 and interleukin-8 (IL-6 and IL-8), angiogenic factors, and vascular endothelial growth factor (VEGF) were determined by the enzyme-linked immunosorbent assay (ELISA). Gap junction intercellular communication (GJIC) was determined by the scrape-load/dye transfer method. The expression levels of protein kinase Cbeta (PKCbeta), connexin 43 (Cx43), transforming growth factor-beta1 (TGF-beta1), and cyclooxygenase-2 (COX-2) were determined by Western blot. Incubation of retinal cells with 10 microM trans-resveratrol in the presence of 5.5 mM glucose did not affect any of the biomarkers investigated. Incubation of ARPE-19 cells with 33 mM glucose for 9 days significantly induced the accumulation of VEGF, IL-6, IL-8, TGF-beta, and COX-2, activation of PKCbeta, and reduction of Cx43 and GJIC. Incubation of ARPE-19 cells with 33 mM glucose in the presence of 0-10 microM trans-resveratrol dose-dependently inhibited VEGF, TGF-beta1, COX-2, IL-6, and IL-8 accumulation, PKCbeta activation, and Cx43 degradation and enhanced GJIC. These data suggest that trans-resveratrol can protect the retinal pigment epithelial cells against hyperglycemia-induced low-grade inflammation and GJIC degradation.
Losso
Jack N
JN
Department of Food Science, Louisiana State University Agricultural Center, Baton Rouge, LA 70803, USA.
Truax
Robert E
RE
Richard
Gerald
G
D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics / Q000276:immunology*; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D000077185:Resveratrol; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000276:immunology*; D013267:Stilbenes / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000276:immunology
D018031:Connexin 43; D015850:Interleukin-6; D016209:Interleukin-8; D013267:Stilbenes; D053773:Transforming Growth Factor beta1; D000077185:Resveratrol