Rk. Kutty et al., INCREASED EXPRESSION OF HEME OXYGENASE-1 IN HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS BY TRANSFORMING GROWTH-FACTOR-BETA, Journal of cellular physiology, 159(2), 1994, pp. 371-378
Antibodies specific for heme oxygenase-1 (HO-1) were produced in rabbi
ts, using the multiple antigen peptide (MAP) technique, and were emplo
yed to investigate the ability of transforming growth factor-beta 1 (T
GF-beta 1) to induce the HO-1 protein in cultured human retinal pigmen
t epithelial (RPE) cells. Western blot analyses showed that the cytoki
ne induced HO-1 in these cells in a time- and dose-dependent manner. T
GF-beta 1 also increased the mRNA for HO-1 in treated cells prior to t
he increase in HO-1 protein. The induction was effectively blocked by
a neutralizing antibody preparation against TGF-beta 1. When tested un
der similar conditions, other growth factors such as basic fibroblast
growth factor-I, platelet-derived growth factor, insulin-like growth f
actor, transforming growth factor-beta, and epidermal growth factor di
d not show appreciable induction of HO-1. Lipopolysaccharide, tumor ne
crosis factor-alpha, and interferon-gamma were also not inducers, alth
ough TGF-beta 2 effectively induced HO-1. Heavy metal ions and thiol r
eagents were also highly potent inducers of HO-1 in human RPE cells. T
he induction of HO-1 by TGF-beta 1 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-beta 1, causing an increase in the expression
of both HO-1 message and protein in specific neuroepithelial and fibro
blast cells. (C) 1994 Wiley-Liss, Inc.*