Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element

Citation
N. Li et al., Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element, J IMMUNOL, 165(6), 2000, pp. 3393-3401
Citations number
54
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
165
Issue
6
Year of publication
2000
Pages
3393 - 3401
Database
ISI
SICI code
0022-1767(20000915)165:6<3393:IOHOEI>2.0.ZU;2-C
Abstract
Diesel exhaust particles (DEP) contain organic chemicals that contribute to the adverse health effects of inhaled particulate matter. Because DEP indu ce oxidative stress in the lung and in macrophages, effective antioxidant d efenses are required. One type of defense is through the expression of the antioxidant enzyme, heme oxygenase I (HO-1). HO-1 as well as phase II detox ifying enzymes are induced via antioxidant response elements (ARE) in their promoters of that gene. We show that a crude DEP total extract, aromatic a nd polar DEP fractions, a benzo(a)pyrene quinone, and a phenolic antioxidan t induce HO-1 expression in RAW264.7 cells in an ARE-dependent manner. N-ac etyl cysteine and the flavonoid, luteolin, inhibited HO-1 protein expressio n. We also demonstrate that the same stimuli induce HO-1 mRNA expression in parallel with the activation of the SX2 enhancer of that gene. Mutation of the ARE core, but not the overlapping AP-1 binding sequence, disrupted SX2 activation. Finally, we show that biological agents, such as oxidized 1-pa lmitoyl-2-arachidonoyl-sn-glycero-3-phosphocoline, could also induce HO-1 e xpression via an ARE-dependent mechanism. Prior induction of HO-1 expressio n, using cobalt-protoporphyrin, protected RAW264.7 cells against DEP-induce d toxicity. Taken together, these data show that HO-1 plays an important ro le in cytoprotection against redox-active DEP chemicals, including quinones .