TY - JOUR
T1 - The effect of clonidine on VEGF expression in human retinal pigment epithelial cells (ARPE-19)
AU - Watanabe, Kazuhiko
AU - Zhang, Xue Yun
AU - Kitagawa, Kiyotaka
AU - Yunoki, Tatsuya
AU - Hayashi, Atsushi
N1 - Funding Information:
Acknowledgments This work was supported in part by a Grant-in-Aid for Scientific Research (No.: 19791259) from the Ministry of Education, Science, Sports, and Culture of Japan.
PY - 2009
Y1 - 2009
N2 - Background: The purpose of this study was to investigate the effect of clonidine, an alpha2-adrenergic receptor (α2 -ADR) agonist, on vascular endothelial growth factor (VEGF) expression and secretion in the human retinal pigment epithelial cell line (ARPE-19) stimulated with interleukin-1β (IL-1β). Methods: Alpha2-ADRs (α2A, α2B, and α2C) mRNA expression in ARPE-19 cells was examined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Clonidine and inhibitors against protein kinases that are involved in the regulation of the intracellular signal transduction were added to serum-free medium before stimulation of IL-1β. The α2-ADR antagonist, Yohimbine, was loaded 30 min before the addition of clonidine. The expression of VEGF mRNA and protein was measured by real-time PCR and enzyme-linked immunosorbent assay. Results: Alpha2A-ADR, α2B-ADR, and α2C-ADR mRNA was expressed in RPE cells. Clonidine, an inhibitor of p38MAPK and MEK1/2, inhibited the expression of VEGF protein and mRNA in the RPE cells stimulated with IL-1β. The inhibitory effect of clonidine on the secretion of VEGF protein stimulated with IL-1β was blocked by β2-ADR antagonists. Conclusions: The effect of clonidine on the expression of VEGF may be via suppression of the p38MAPK and MEK1/2 signal transduction pathways activated with IL-1β.
AB - Background: The purpose of this study was to investigate the effect of clonidine, an alpha2-adrenergic receptor (α2 -ADR) agonist, on vascular endothelial growth factor (VEGF) expression and secretion in the human retinal pigment epithelial cell line (ARPE-19) stimulated with interleukin-1β (IL-1β). Methods: Alpha2-ADRs (α2A, α2B, and α2C) mRNA expression in ARPE-19 cells was examined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Clonidine and inhibitors against protein kinases that are involved in the regulation of the intracellular signal transduction were added to serum-free medium before stimulation of IL-1β. The α2-ADR antagonist, Yohimbine, was loaded 30 min before the addition of clonidine. The expression of VEGF mRNA and protein was measured by real-time PCR and enzyme-linked immunosorbent assay. Results: Alpha2A-ADR, α2B-ADR, and α2C-ADR mRNA was expressed in RPE cells. Clonidine, an inhibitor of p38MAPK and MEK1/2, inhibited the expression of VEGF protein and mRNA in the RPE cells stimulated with IL-1β. The inhibitory effect of clonidine on the secretion of VEGF protein stimulated with IL-1β was blocked by β2-ADR antagonists. Conclusions: The effect of clonidine on the expression of VEGF may be via suppression of the p38MAPK and MEK1/2 signal transduction pathways activated with IL-1β.
KW - ARPE-19 cell
KW - Clonidine
KW - Vascular endothelial growth factor
KW - Yohimbine
KW - α-adrenergic receptor
UR - http://www.scopus.com/inward/record.url?scp=57949091193&partnerID=8YFLogxK
U2 - 10.1007/s00417-008-0990-5
DO - 10.1007/s00417-008-0990-5
M3 - 学術論文
C2 - 19011889
AN - SCOPUS:57949091193
SN - 0721-832X
VL - 247
SP - 207
EP - 213
JO - Graefe's Archive for Clinical and Experimental Ophthalmology
JF - Graefe's Archive for Clinical and Experimental Ophthalmology
IS - 2
ER -