Positive and negative regulation of the human heme oxygenase-1 gene expression in cultured cells

Takahashi, Shigeru; Takahashi, Yûji; Ito, Kazumi; Nagano, Tadahiro; Shibahara, Shigeki; Miura, Takashi

doi:10.1016/s0167-4781(99)00156-6

Cited by 35 publications

(35 citation statements)

References 15 publications

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“…To determine HO-1 promoter activity, the HO-1-luc construct (Ref. 26; a kind gift of Shigeru Takahashi, Scripps Research Institute, La Jolla, CA; 10 g) was transfected together with a pCMV-␤GAL construct (10 g) by electroporation (0.35 kV, 960 F, Gene Pulser; Bio-Rad, Hercules, CA) into Ton.B210-X cells (1 ϫ 10 7 in 800 l). Thereafter, cells were either maintained in the presence or absence of doxycycline (1 g/ml) for 18 h in UltraCulture medium.…”

Section: Methodsmentioning

confidence: 99%

Identification of Heme Oxygenase-1 As a Novel BCR/ABL-Dependent Survival Factor in Chronic Myeloid Leukemia

Mayerhofer¹,

Florian²,

Krauth³

et al. 2004

Cancer Research

146

171

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Section: Methodsmentioning

confidence: 99%

Identification of Heme Oxygenase-1 As a Novel BCR/ABL-Dependent Survival Factor in Chronic Myeloid Leukemia

Mayerhofer¹,

Florian²,

Krauth³

et al. 2004

Cancer Research

146

171

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show abstract

“…Consensus binding sites for oxidative stress-responsive transcription factors, including nuclear factor-B (NF-B), activator protein-1 (AP-1), AP-2, Sp1, upstream stimulatory factor, c-myc/max and interleukin-6 response elements have been reported in the promoter region of the human HO-1 gene (Deramaudt et al, 1999;Lavrovsky et al, 1994;Muraosa et al, 1996;Sato et al, 1990;Tyrrell et al, 1993), suggesting a potential role for these factors in modulating HO-1 induction. Positive regulatory regions of the human HO-1 promoter contain consensus binding sites for AP-1, STATx, c-Rel, hepatocyte nuclear factor-1 and factor-4, GATA-X, and cadmium response element (Takahashi et al, 1999b andTakeda et al, 1994). Negative regulatory regions of the human HO-1 promoter contain consensus binding sites for negative regulatory elements (NRE) boxes (Takahashi et al, 1999b) and a polymorphic GT repeat region (Yamada et al, 2000).…”

Section: A Primary Structure Of Different Heme Oxygenase Isoformsmentioning

confidence: 99%

Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications

Wang²

2005

Pharmacol Rev

853

741

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“…Reporter assays were performed with vector constructs containing 4000 base pairs, 2782 base pairs, or 1976 base pairs of the human HO-1 promoter fused to a firefly luciferase gene (Takahashi et al, 1999). The signal transducer and activator of transcription (STAT) 3 point mutation was created with the QuikChange II site-directed mutagenesis kit (Stratagene, La Jolla, CA).…”

Section: Reporter Analysismentioning

confidence: 99%

Heme Oxygenase-1 Contributes to an Alternative Macrophage Activation Profile Induced by Apoptotic Cell Supernatants

Weis

Weigert

Knethen

et al. 2009

MBoC

152

128

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Apoptotic cells (AC) are rapidly engulfed by professional phagocytes such as macrophages to avoid secondary necrosis and thus inflammation. Recognition of AC polarizes macrophages toward an anti-inflammatory phenotype, which shows homology to an alternatively activated M2 macrophage. However, mechanistic details provoking these phenotype alterations are incompletely understood. Here, we demonstrate a biphasic up-regulation of heme oxygenase-1 (HO-1), a protein that bears an antiapoptotic as well as an anti-inflammatory potential, in primary human macrophages, which were exposed to the supernatant of AC. Although the first phase of HO-1 induction at 6 h was accomplished by AC-derived sphingosine-1-phosphate (S1P) acting via S1P receptor 1, the second wave of HO-1 induction at 24 h was attributed to autocrine signaling of vascular endothelial growth factor A (VEGFA), whose expression and release were facilitated by S1P. Whereas VEGFA release from macrophages was signal transducer and activator of transcription (STAT) 1-dependent, vascular endothelial growth factor itself triggered STAT1/STAT3 heterodimer formation, which bound to and activated the HO-1 promoter. Knockdown of HO-1 proved its relevance in facilitating enhanced expression of the antiapoptotic proteins Bcl-2 and Bcl-X L , as well as the anti-inflammatory adenosine receptor A 2A . These findings suggest that HO-1, which is induced by AC-derived S1P, is critically involved in macrophage polarization toward an M2 phenotype.

show abstract

Positive and negative regulation of the human heme oxygenase-1 gene expression in cultured cells

Cited by 35 publications

References 15 publications

Identification of Heme Oxygenase-1 As a Novel BCR/ABL-Dependent Survival Factor in Chronic Myeloid Leukemia

Identification of Heme Oxygenase-1 As a Novel BCR/ABL-Dependent Survival Factor in Chronic Myeloid Leukemia

Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications

Heme Oxygenase-1 Contributes to an Alternative Macrophage Activation Profile Induced by Apoptotic Cell Supernatants

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