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

J Cell Physiol. 1994 May;159(2):371-8. doi: 10.1002/jcp.1041590221.

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-beta 1 (TGF-beta 1) 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-beta 1 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-beta 1. When tested under similar conditions, other growth factors such as basic fibroblast growth factor-I, platelet-derived growth factor, insulin-like growth factor, transforming growth factor-alpha, and epidermal growth factor did not show appreciable induction of HO-1. Lipopolysaccharide, tumor necrosis factor-alpha, and interferon-gamma were also not inducers, although TGF-beta 2 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-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 fibroblast cells.

MeSH terms

  • Amino Acid Sequence
  • Cells, Cultured
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Humans
  • Immunochemistry
  • Molecular Sequence Data
  • Osmolar Concentration
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / enzymology*
  • Polymerase Chain Reaction
  • Time Factors
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Transforming Growth Factor beta
  • Heme Oxygenase (Decyclizing)