Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, reduces chemokines and adhesion molecule expression induced by IL-1β in human corneal fibroblasts.

PURPOSE: Dehydroxymethylepoxyquinomicin (DHMEQ) is derived from the antibiotic, epoxyquinomicin C, and is a novel low molecular weight nuclear factor-κB (NF-κB) inhibitor. We investigated the effects of DHMEQ on the expression of chemokines and the intercellular adhesion molecule (ICAM)-1 induced by proinflammatory cytokines in cultures of the human corneal fibroblasts (HCFs).
METHODS: The cytotoxicity of DHMEQ on cultured HCFs was evaluated by cell proliferation assays. Cultures were exposed to interleukin (IL)-1β, and the production of IL-8 and monocyte chemoattractant protein (MCP)-1 was assessed by enzyme-linked immunosorbent assay. The degree of expression of ICAM-1 was measured by flow cytometry. The translocation of NF-κB p65 into the nucleus of HCFs was assessed by immunocytochemistry.
RESULTS: DHMEQ was not toxic to cultured HCFs at doses up to 10 μg/ml. DHMEQ significantly suppressed the production of both IL-8 and MCP-1 in IL-1β-stimulated HCFs. In addition, DHMEQ down-regulated ICAM-1 expression in IL-1β-stimulated HCFs in a dose-dependent manner. DHMEQ inhibited the IL-1β-induced nuclear accumulation of p65, a component of NF-κB, in HCFs.
CONCLUSIONS: The suppression of inflammatory chemokines IL-8 and MCP-1 and inhibition of the expression of ICAM-1 in cultured HCFs by DHMEQ indicates that DHMEQ may have a therapeutic potential for treating ICAM-1 and chemokine-mediated corneal inflammatory disorders.