Role of monocyte chemotactic protein-1 and nuclear factor kappa B in the pathogenesis of proliferative diabetic retinopathy.
Intraocular concentrations of monocyte chemotactic protein-1 (MCP-1) are increased in proliferative diabetic retinopathy (PDR). Nuclear factor kappa B (NF-kappaB) is a transcription factor, and NF-kappaB binding site is located in gene promoter of MCP-1. This study was conducted to investigate the potential role of MCP-1 and NF-kappaB in the pathogenesis of PDR. Epiretinal membrane (ERM) samples were obtained during vitrectomy from 19 eyes with PDR and 16 eyes with idiopathic ERM. They were processed for RT-PCR analysis. Four PDR ERMs were processed for immunohistochemical analysis. In addition, cultured Müller glial cells were stimulated with glycated albumin or high glucose. After the stimulation, we examined nuclear localization of NF-kappaB p50, MCP-1 promoter activity, and MCP-1 concentration in culture media. MCP-1 mRNA expression was significantly higher in PDR (74%) than in idiopathic ERMs (38%) (P < 0.05). Immunohistochemical analysis revealed that MCP-1 protein is colocalized with active form of NF-kappaB p50. In vitro studies demonstrated that glycated albumin or high glucose induces NF-kappaB activation followed by up-regulation of MCP-1 promoter activity and protein production in glial cells. These results suggest that MCP-1, under the regulation of NF-kappaB, is involved in the pathogenesis of PDR.
Harada
Chikako
C
Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan.
Okumura
Akinori
A
Namekata
Kazuhiko
K
Nakamura
Kazuaki
K
Mitamura
Yoshinori
Y
Ohguro
Hiroshi
H
Harada
Takayuki
T
D000328:Adult; D000368:Aged; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D019773:Epiretinal Membrane / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology; D000093423:Glycated Serum Albumin
D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D012333:RNA, Messenger; D012709:Serum Albumin; D005947:Glucose; D000093423:Glycated Serum Albumin