Heme Oxygenase-1 Modulates the Expression of Adhesion Molecules Associated with Endothelial Cell Activation

Soares, Miguel P.; Seldon, Mark P.; Grégoire, Isabel Pombo; Vassilevskaia, Tatiana; Berberat, Pascal O.; Yu, Jia; Tsui, Ting Y.; Bach, Fritz H.

doi:10.4049/jimmunol.172.6.3553

Cited by 419 publications

(322 citation statements)

References 49 publications

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“…29 In endothelial cells, modulation of HO-1 activity by Nrf2 inhibited NF-kBemediated transcription of vascular cell adhesion molecule-1 and E-selectin. 40 Induction of Nrf2 signaling in mouse peritoneal macrophages reduces lipopolysaccharide-mediated induction of cyclooxygenase 2, tumor necrosis factor-a, and IL-1b expression. 41 In response to acute lung injury, deletion of Nrf2 was associated with impaired resolution of inflammation.…”

Section: Nrf2 In Cellular Redox Homeostasismentioning

confidence: 99%

Nuclear Factor–Erythroid-2–Related Factor 2 in Aging and Lung Fibrosis

Swamy

Rajasekaran

Thannickal

2016

The American Journal of Pathology

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Aging and age-related diseases have been associated with elevated oxidative stress, which may be related to increased production of reactive species and/or a deficiency in antioxidant defenses. The nuclear factor-erythroid-2erelated factor 2 (Nrf2)-mediated antioxidant response pathway maintains cellular reduction-oxidation homeostasis by inducing the transcription of an array of cytoprotective genes. However, there is evidence of impaired Nrf2 response in aging contributing to age-related fibrotic diseases. Herein, we review mechanisms for the dysregulation of Nrf2 signaling in aging. This understanding will pave the way for the design of novel therapeutic strategies that restore Nrf2 signaling to reestablish cellular homeostasis in aging and age-related fibrotic diseases.

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Section: Nrf2 In Cellular Redox Homeostasismentioning

confidence: 99%

Nuclear Factor–Erythroid-2–Related Factor 2 in Aging and Lung Fibrosis

Swamy

Rajasekaran

Thannickal

2016

The American Journal of Pathology

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“…7,8 In order to assess if ARE-driven HO-1 expression can have antiinflammatory effects in endothelial cells, we first examined its effect on NF-kB activation assessed by the activation of the NF-kB-regulated luciferase-reporter construct. To this end, cells were transduced with either an empty lentiviral control vector having only the phosphoglycerate kinase (PGK) promoter but no transgene, or 2 Â GCLM-HO-1 vector together with the NFkB-luciferase-reporter construct.…”

Section: Lentiviral Transduction Of Are-ho-1 Decreases the Induction mentioning

confidence: 99%

“…In endothelial cells, adenoviral overexpression of HO-1 has been shown to inhibit tumor necrosis factor (TNF)-a-induced activation of nuclear factor (NF)-kB and vascular cell adhesion molecule-1 (VCAM-1) expression. 7,8 For an optimal therapeutic response, it would be beneficial if the transgene expression could be regulated in order to turn the gene expression on and off when needed. This can be accomplished through the use of promoters that can be activated by orally administered drugs, such as tetracycline.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress-inducible lentiviral vectors for gene therapy

Hurttila

Kansanen

et al. 2008

Gene Ther

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Oxidative stress is important in several pathologies, including cardiovascular diseases such as atherosclerosis and cardiac ischemia-reperfusion injury. An important mechanism for adaptation to oxidative stress is induction of genes through the antioxidant response element (ARE), which regulates the expression of antioxidant and cytoprotective genes via the transcription factor Nrf2 (nuclear factor E2-related factor 2). As Nrf2-regulated genes are induced during oxidant stress occurring, for example, in reperfusion after ischemia, we took a novel approach to exploit ARE for the development of oxidative stress-inducible gene therapy vectors. To this end, one, two or three ARE-containing regions from human NAD(P)H:quinone oxidoreductase-1, glutamate-cysteine ligase modifier subunit and mouse heme oxygenase-1 were cloned into a vector expressing luciferase under a minimal SV40 promoter. The construct, which was the most responsive to ARE-inducing agents, was chosen for further studies in which a lentiviral vector was produced for an efficient transfer to endothelial cells. Heme oxygenase-1 (HO-1), which has well-characterized anti-inflammatory properties, was used as the therapeutic transgene. In human endothelial cells, AREdriven HO-1 overexpression inhibited nuclear factor-kB activation and subsequent vascular cell adhesion molecule-1 expression induced by tumor necrosis factor-a. We conclude that the ARE element is a promising alternative for the development of oxidative stress-inducible gene therapy vectors.

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“…48 Indeed, numerous recent observations point to a potential role of HO-1 in the downregulation of proinflammatory cytokine expression at the site of inflammation in various model systems. [49][50][51][52][53] It has also been shown that HO-1 might provide an anti-inflammatory action in vivo through the downmodulation of cell adhesion molecules accompanied by inhibition of leukocyte infiltration, [54][55][56] and via promotion of noninflammatory angiogenesis facilitating tissue repair. 56 Moreover, an increased leukocyte adhesion to the vascular wall and spontaneous perivascular infiltration of leukocytes in various tissues of HO-1-deficient mice has been reported before.…”

Section: Expression Of Il-6 After To Administration and Its Possible mentioning

confidence: 99%

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6

Tron¹,

Novosyadlyy²,

Dudás³

et al. 2005

Laboratory Investigation

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Heme oxygenase-1 (HO-1) is the inducible isoform of an enzyme family responsible for heme degradation and was suggested to be involved in the acute phase response in the liver. However, the mechanisms of the HO-1 regulation under inflammatory conditions are poorly understood. Therefore, the purpose of the current work was to study the expression of HO-1 in the liver and other organs of rats with a localized inflammation after intramuscular injection of turpentine oil (TO). Since interleukin-6 (IL-6) is known to be a principal mediator of inflammation, the levels of this cytokine were also estimated in the animal model used. HO-1 and IL-6 expression was evaluated by Northern blot, in situ hybridization, Western blot, immunohistochemistry and enzyme-linked immunosorbent assay. In the liver and injured muscle, the HO-1 mRNA levels were dramatically increased 4-6 h after TO administration. HO-1 protein levels in the liver were elevated starting from 6-12 h after the treatment. In other internal organs such as the heart, kidney and large intestine, only a slight induction of HO-1 mRNA was observed. IL-6-specific transcripts appeared only in the injured muscle and were in accordance with serum levels of IL-6. In turn, temporal expression of IL-6 in the muscle and circulatory IL-6 levels correlated well with HO-1 expression in the liver and injured muscle. In the liver of control rats HO-1 protein was detected in Kupffer cells, while in TO-injected rats also hepatocytes became strongly HO-1 positive. Conversely, in the injured muscle, HO-1 immunoreactivity was attributed only to macrophages. Our data demonstrate that during localized inflammation HO-1 expression was rapidly and strongly induced in macrophages of injured muscle and in hepatocytes, and IL-6 derived from injured muscle seems to be responsible for the HO-1 induction in the liver.

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Heme Oxygenase-1 Modulates the Expression of Adhesion Molecules Associated with Endothelial Cell Activation

Cited by 419 publications

References 49 publications

Nuclear Factor–Erythroid-2–Related Factor 2 in Aging and Lung Fibrosis

Nuclear Factor–Erythroid-2–Related Factor 2 in Aging and Lung Fibrosis

Oxidative stress-inducible lentiviral vectors for gene therapy

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6

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