Overexpression of HO-1 protects against TNF-α-mediated airway inflammation by down-regulation of TNFR1-dependent oxidative stress

I-Ta Lee, Shue Fen Luo, Chiang Wen Lee, Shyi Wu Wang, Chih Chung Lin, Chia Chi Chang, Yuh Lien Chen, Lee Young Chau, Chuen Mao Yang

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Oxidative stresses are believed to play an important role in the induction of both cell adhesion molecules and pro-inflammatory cytokines, a key event in a variety of inflammatory processes. The enzyme heme oxygenase-1 (HO-1) functions as an antioxidant and serves to protect against tissue injury. In this study, we report that HO-1 was induced in cultured human tracheal smooth muscle cells after either treatment with a potent inducer of HO-1 activity, cobalt protoporphyrin IX, or infection with a recombinant adenovirus that carries the human HO-1 gene. Overexpression of HO-1 protected against tumor necrosis factor (TNF)-α-mediated airway inflammation via the down-regulation of oxidative stress, adhesion molecules, and interleukin-6 in both cultured human tracheal smooth muscle cells and the airways of mice. In addition, HO-1 overexpression inhibited TNF-α-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, adherence of THP-1 cells, generation of interleukin-6, p47phox translocation, and nuclear factor-κB activation. HO-1 overexpression also attenuated TNF-α-induced oxidative stress, which was abrogated in the presence of both the HO-1 inhibitor, zinc protoporphyrin IX, as well as a carbon monoxide scavenger. In addition, HO-1 overexpression reduced the formation of a TNFR1/c-Src/p47phox complex. These results suggest that HO-1 functions as a suppressor of TNF-α signaling, not only by inhibiting the expression of adhesion molecules and generation of interleukin-6, but also by diminishing intracellular reactive oxygen species production and nuclear factor-κB activation in both cultured human tracheal smooth muscle cells and the airways of mice.

Original languageEnglish
Pages (from-to)519-532
Number of pages14
JournalAmerican Journal of Pathology
Volume175
Issue number2
DOIs
Publication statusPublished - Jan 1 2009
Externally publishedYes

Fingerprint

Receptors, Tumor Necrosis Factor, Type I
Heme Oxygenase-1
Oxidative Stress
Down-Regulation
Tumor Necrosis Factor-alpha
Inflammation
Smooth Muscle Myocytes
Interleukin-6
Human Adenoviruses
Vascular Cell Adhesion Molecule-1
Cell Adhesion Molecules
Intercellular Adhesion Molecule-1
Carbon Monoxide
Reactive Oxygen Species
Antioxidants

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Overexpression of HO-1 protects against TNF-α-mediated airway inflammation by down-regulation of TNFR1-dependent oxidative stress. / Lee, I-Ta; Luo, Shue Fen; Lee, Chiang Wen; Wang, Shyi Wu; Lin, Chih Chung; Chang, Chia Chi; Chen, Yuh Lien; Chau, Lee Young; Yang, Chuen Mao.

In: American Journal of Pathology, Vol. 175, No. 2, 01.01.2009, p. 519-532.

Research output: Contribution to journalArticle

Lee, I-Ta ; Luo, Shue Fen ; Lee, Chiang Wen ; Wang, Shyi Wu ; Lin, Chih Chung ; Chang, Chia Chi ; Chen, Yuh Lien ; Chau, Lee Young ; Yang, Chuen Mao. / Overexpression of HO-1 protects against TNF-α-mediated airway inflammation by down-regulation of TNFR1-dependent oxidative stress. In: American Journal of Pathology. 2009 ; Vol. 175, No. 2. pp. 519-532.
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