Anti‑inflammatory effects of the NF‑κB inhibitor dehydroxymethylepoxyquinomicin on ARPE‑19 cells

Abstract

The retinal pigment epithelium (RPE) is a polarized, monolayer of pigmented cells that forms the outer retinal layer. A key function of the RPE is to maintain the integrity of the photoreceptors mainly via phagocytosis and recycling of the digested photoreceptor outer segments. Moreover, RPE cells are a major source of inflammatory cytokines and chemokines, which play important roles in the activation of other immune cells under inflammatory conditions in the posterior segment of the eye. Dehydroxymethylepoxyquinomicin (DHMEQ) is a NF-κB inhibitor and its structure is related to that of epoxyquinomicin C, which is an antibiotic. The present study evaluated the anti‑inflammatory effects of DHMEQ on a human retinal pigment epithelial cell line (ARPE-19). It was revealed that high concentrations of DHMEQ (100 µg/ml) induced apoptosis and necrosis of tumor necrosis factor (TNF)-α-stimulated ARPE-19 cells. Furthermore, the percentage of intercellular adhesion molecule 1 (ICAM-1)-positive TNF-α-stimulated cells was significantly reduced in the presence of DHMEQ (10 µg/ml), as determined by flow cytometry. It was also demonstrated that DHMEQ exposure significantly decreased the levels of interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1) in the supernatant of cultured ARPE-19 cells as determined by ELISA. Moreover, the protein expression levels of IL-8 and MCP-1 were significantly reduced in ARPE-19 cells exposed to DHMEQ compared with cells exposed to dexamethasone. PCR array analysis revealed that DHMEQ reduced the expression levels of MCP-1, ICAM-1, IL-6, Toll-like receptor (TLR)2, TLR3 and TLR4. Therefore, the present results indicated that DHMEQ has anti‑inflammatory effects on TNF-α-stimulated ARPE-19 cells. Thus, DHMEQ may have therapeutic potential for TNF-α-mediated inflammatory disorders of the eye.