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Journal of Histochemistry and Cytochemistry, Vol. 46, 429-436, April 1998, Copyright © 1998, The Histochemical Society, Inc.

ARTICLE

The Role of NF-{kappa}B in Retinal Neovascularization in the Rat: Possible Involvement of Cytokine-induced Neutrophil Chemoattractant (CINC), a Member of the Interleukin-8 Family

Ayako Yoshidaa, Shigeo Yoshidaa, Yasuaki Hataa, Ahmad K. Khalila, Tatsuro Ishibashia, and Hajime Inomataa
a Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan

Correspondence to: Ayako Yoshida, Dept. of Ophthalmology, Faculty of Medicine, Kyushu Univ., Fukuoka 812-82, Japan.

Hypoxia precedes neovascularization in many retinal diseases that can lead to irreversible vision loss. The transcription factor NF-{kappa}B is activated by hypoxia and regulates the expression of many genes, including angiogenic factors. The relation between the NF-{kappa}B 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-{kappa}B and CINC immunoreactivity was detected in retinal glial cells in the nonperfused retina and in neovascular cells. Activated NF-{kappa}B was detected before the CINC staining, and both of these events occurred before the development of neovascularization. The intensity of both activated NF-{kappa}B 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-{kappa}B 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-{kappa}B results in CINC production and participates in the induction of retinal neovascularization. (J Histochem Cytochem 46:429–436, 1998)

Key Words: NF-{kappa}B, cytokine-induced neutrophil, chemoattractant, immunohistochemistry, RT-PCR, rat, glial cells


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