Prolonged cigarette smoke exposure decreases heme oxygenase-1 and alters Nrf2 and Bach1 expression in human macrophages: Roles of the MAP kinases ERK 1/2 and JNK

• Published in: FEBS letters Vol. 583; no. 21; pp. 3508 - 3518
• Main Authors: Goven, D., Boutten, A., Leçon-Malas, V., Boczkowski, J., Bonay, M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 03.11.2009
• Subjects: BTB and CNC homology 1, basic leucine zipper transcription factor 1; Cigarette smoke; Heme oxygenase; Kelch-like ECH-associated protein 1; Macrophage; Nuclear factor erythroid 2-related factor 2; NQO1; Bach1; Kelch-like ECH-associated protein 1; DMSO; JNK; HO; Heme oxygenase; mRNA; MAPK; Nuclear factor erythroid 2-related factor 2; CS; H 2O 2; ARE; 4-HNE; TNF-α; Nrf2; RT-PCR; Keap1; ERK 1/2; BTB and CNC homology 1, basic leucine zipper transcription factor 1; IL1-β; Cigarette smoke; COPD; Macrophage
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2009.10.010

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 kinase 1/2 (ERK 1/2) 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 ERK 1/2 and JNK are involved in CS-induced biphasic HO-1 expression by a specific regulation of Nrf2/Keap1–Bach1.