期刊
FEBS LETTERS
卷 583, 期 21, 页码 3508-3518出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2009.10.010
关键词
Cigarette smoke; Macrophage; Heme oxygenase; Nuclear factor erythroid 2-related factor 2; Kelch-like ECH-associated protein 1; BTB and CNC homology 1, basic leucine zipper transcription factor 1
资金
- Societe de Pneumologie de Langue Fran aise (SPLF)
- Center d'Assistance Respiratoire a Domicile d'Ile de France (CARDIF)
- BoehringerIngelheim
- Chancellerie des Universites de Paris (Legs Poix)
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 (6 h) followed by decreased HO-1 expression concomitantly with nuclear Nrf2/Bach1 ratio decrease (72 h). 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. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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