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- Title
Prolonged cigarette smoke exposure decreases heme oxygenase-1 and alters Nrf2 and Bach1 expression in human macrophages: Roles of the MAP kinases ERK<sub>1/2</sub> and JNK
- Authors
Goven, D.; Boutten, A.; Leçon-Malas, V.; Boczkowski, J.; Bonay, M.
- Abstract
Abstract: Tobacco may be involved in the decreased macrophage heme oxygenase-1 (HO-1) expression described in smoking-induced severe emphysema, via the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)–BTB and CNC homology 1, basic leucine zipper transcription factor 1 (Bach1) pathway. We assessed in vitro effects of cigarette smoke condensate (CS) in the human monocyte/macrophage cell line (THP-1). CS exposure led to increased HO-1 and nuclear Nrf2 expression (6h) followed by decreased HO-1 expression concomitantly with nuclear Nrf2/Bach1 ratio decrease (72h). CS-induced mitogen-activated protein kinase (MAPK) phosphorylation. Extracellular-signal-regulated kinase1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK) inhibition completely abrogated CS effects on HO-1 expression and nuclear Nrf2/Bach1 translocation. These results suggest that ERK1/2 and JNK are involved in CS-induced biphasic HO-1 expression by a specific regulation of Nrf2/Keap1–Bach1.
- Subjects
CIGARETTE smoke; HEME oxygenase; MACROPHAGES; LEUCINE zippers; TUMOR necrosis factors; HYDROGEN peroxide; LUNG diseases; DIMETHYL sulfoxide; PROTEIN kinases
- Publication
FEBS Letters, 2009, Vol 583, Issue 21, p3508
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2009.10.010