title: The role of NF-kappaB in retinal neovascularization in the rat. Possible involvement of cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 family.
abstract: Hypoxia precedes neovascularization in many retinal diseases that can lead to irreversible vision loss. The transcription factor NF-kappaB is activated by hypoxia and regulates the expression of many genes, including angiogenic factors. The relation between the NF-kappaB activation and the cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 (IL-8) family, was investigated by immunohistochemistry in a rat model of proliferative retinopathy presumably caused by relative hypoxia. Activated NF-kappaB and CINC immunoreactivity was detected in retinal glial cells in the nonperfused retina and in neovascular cells. Activated NF-kappaB was detected before the CINC staining, and both of these events occurred before the development of neovascularization. The intensity of both activated NF-kappaB and CINC staining remained increased during the development of neovascularization and then declined as neovascularization regressed. In rat retinal glial cells in vitro, dexamethasone, an inhibitor of NF-kappaB activation, prevented the hypoxia-induced increase in the amount of CINC mRNA. Furthermore, CINC induced neovascularization in a rat corneal pocket model. These results suggest that hypoxia-induced activation of NF-kappaB results in CINC production and participates in the induction of retinal neovascularization.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Hata
authors.forename: A K
authors.initials: AK
authors.lastname: Khalil
authors.forename: T
authors.initials: T
authors.lastname: Ishibashi
authors.forename: H
authors.initials: H
authors.lastname: Inomata
mesh_terms: D000199:Actins / Q000378:metabolism; D000332:Aerobiosis; D000693:Anaerobiosis; D000792:Angiography; D000818:Animals; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005128:Eye Diseases / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000199:Actins; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D005904:Glial Fibrillary Acidic Protein; D006131:Growth Inhibitors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014841:von Willebrand Factor; D016222:Fibroblast Growth Factor 2; D003907:Dexamethasone