Amelioration of endotoxin-induced uveitis treated with an IκB

Endotoxin-induced uveitis (EIU) is an animal model of acute anterior segment intraocular inflammation induced by injection of endotoxin, the lipopolysaccharide (LPS) compo-nent of the Gram-negative bacterial cell wall [1]. Cellular infiltration and protein leakage into the anterior chamber of the eye reach a maximum at 24 h after LPS injection [2]. Elevated expression of cytokines and chemokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and macrophage inflam-matory protein (MIP)-2 have been observed concomitant with maximum EIU [2,3]. Other inflammatory mediators, such as nitric oxide [4] and prostaglandin [5], are also involved in the pathogenesis of EIU. The production and release of inflammatory cytokines by LPS depend on inducible gene expression, mediated by the activation of transcription factors. Nuclear factor (NF) κB, one of the most ubiquitous transcription factors, has been suggested to play a key role in these reactions [6]. NFκB exists in the cytoplasm in an inac-tive form, associated with regulatory proteins called inhibi-tors of κB (IκB). Phosphorylation of IκB, an important step in NFκB activation, is mediated by an IκB kinase (IKK). Th