Open AccessThe Role of NF-κB in Retinal Neovascularization in the Rat: Possible Involvement of Cytokine-induced Neutrophil Chemoattractant (CINC), a Member of the Interleukin-8 Family
Author(s) -
Ayako Yoshida,
Shigeo Yoshida,
Yoshinobu Hata,
Ahmad Khalil,
Tatsuro Ishibashi,
Hajime Inomata
Publication year - 1998
Publication title -
journal of histochemistry and cytochemistry/the journal of histochemistry and cytochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.971
H-Index - 124
eISSN - 1551-5044
pISSN - 0022-1554
DOI - 10.1177/002215549804600402
Subject(s) - neovascularization , retina , hypoxia (environmental) , retinal , cytokine , interleukin 8 , chemotaxis , biology , endocrinology , medicine , immunology , chemistry , angiogenesis , receptor , biochemistry , neuroscience , organic chemistry , oxygen
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.