Increased expression of heme oxygenase‐1 in human retinal pigment epithelial cells by transforming growth factor‐β

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Abstract
Antibodies specific for heme oxygenase‐1 (HO‐1) were produced in rabbits, using the multiple antigen peptide (MAP) technique, and were employed to investigate the ability of transforming growth factor‐β1 (TGF‐β1) to induce the HO‐1 protein in cultured human retinal pigment epithelial (RPE) cells. Western blot analyses showed that the cytokine induced HO‐1 in these cells in a time‐ and dose‐dependent manner. TGF‐β1 also increased the mRNA for HO‐1 in treated cells prior to the increase in HO‐1 protein. The induction was effectively blocked by a neutralizing antibody preparation against TGF‐β1. When tested under similar conditions, other growth factors such as basic fibroblast growth factor‐I, plateletderived growth factor, insulin‐like growth factor, transforming growth factor‐α, and epidermal growth factor did not show appreciable induction of HO‐1. Lipopolysaccharide, tumor necrosis factor‐α, and interferon‐γ were also not inducers, although TGF‐β2 effectively induced HO‐1. Heavy metal ions and thiol reagents were also highly potent inducers of HO‐1 in human RPE cells. The induction of HO‐1 by TGF‐β1 was also observed in bovine choroid fibroblasts, but not in HELA, HEL or bovine corneal fibroblasts. Our results demonstrate for the first time that HO‐1 can be induced by an important cytokine, TGF‐β1, causing an increase in the expression of both HO‐1 message and protein in specific neuroepithelial and fibroblast cells. © 1994 wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.