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

✍ Scribed by R. Krishnan Kutty; Chandrasekharam N. Nagineni; Geetha Kutty; John J. Hooks; Gerald J. Chader; Barbara Wiggert

Publisher
John Wiley and Sons
Year
1994
Tongue
English
Weight
929 KB
Volume
159
Category
Article
ISSN
0021-9541

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✦ Synopsis

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-pl (TGF-P1) 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 dosedependent manner. TGF-PI 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-Pl. 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-a, and epidermal growth factor did not show appreciable induction of HO-1. Lipopolysaccharide, tumor necrosis factor-a, and interferon-y were also not inducers, although TGF-P2 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-P1 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-P1, causing an increase in the expression of both HO-1 message and protein in specific neuroepithelial and fibroblast cells.

01994 WiIey-Liss, tnc.**

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