Protective effects of heme oxygenase-1 against oxidant-induced injury in the cultured human tracheal epithelium

Norihiro Yamada, Mutsuo Yamaya, Shoji Okinaga, Ria Lie, Tomoko Suzuki, Katsutoshi Nakayama, Atsushi Takeda, Tokio Yamaguchi, Yasuto Itoyama, Kiyohisa Sekizawa, Hidetada Sasaki

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51 Citations (Scopus)

Abstract

To examine whether increases in heme oxygenase (HO)-1 activity have protective effects on the oxidant-induced injury of airway epithelial cells, human tracheal epithelial cells were cultured on a porous filter membrane, and electrical conductance (G) and mannitol flux across epithelial membrane were measured with Ussing's chamber methods and D-[ 3 H]mannitol, respectively. Hydrogen peroxide (H 2 O 2 ; 1 mM) increased G with time from the baseline value of 6.0 ± 0.6 to 17.8 ± 0.9 mS/cm 2 at 6 h after administration (P < 0.001). Likewise, H 2 O 2 significantly increased mannitol flux through the cultured epithelium (P < 0.01). Pretreatment of cultured epithelial cells with hemin (10 μM; 8 h) or interleukin (IL)-1β (10 ng/ml; 16 h) completely inhibited increases in G and mannitol flux induced by H 2 O 2 . Tin protoporphyrin IX (50 μm) and zinc protoporphyrin IX (10 μM), inhibitors of HO-1, reduced hemin-induced and IL-1β-induced inhibitory effects. Hemin treatment increased HO-1 messenger RNA expression, HO-1 protein production, and HO activity and bilirubin content as well as ferritin content in the cultured epithelial cells. Pretreatment with hemin and desferoxamine, which, like ferritin, can bind iron, inhibited H 2 O 2 -induced increases in G and mannitol permeability. Although exogenous bilirubin mimicked hemin-induced inhibitory effects, exogenous apoferritin failed to inhibit H 2 O 2 -induced effects on G and mannitol permeability. These findings suggest that HO-1 induction provides protection against H 2 O 2 -induced injury of the cultured human airway epithelial cells in part via the HO-bilirubin pathway.

Original languageEnglish
Pages (from-to)428-435
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume21
Issue number3
DOIs
Publication statusPublished - 1999 Jan 1

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Yamada, N., Yamaya, M., Okinaga, S., Lie, R., Suzuki, T., Nakayama, K., Takeda, A., Yamaguchi, T., Itoyama, Y., Sekizawa, K., & Sasaki, H. (1999). Protective effects of heme oxygenase-1 against oxidant-induced injury in the cultured human tracheal epithelium. American journal of respiratory cell and molecular biology, 21(3), 428-435. https://doi.org/10.1165/ajrcmb.21.3.3501