Haem oxygenase-1 in inflammation

2004 ◽  
Vol 32 (6) ◽  
pp. 1093-1094 ◽  
Author(s):  
S.A. Rushworth ◽  
M.A. O'Connell
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Nuclear Factor Κb ◽  
Protective Role ◽  
Related Factor ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Inflammatory Stimuli ◽  
Haem Oxygenase ◽  
Flanking Region

HO-1 (haem oxygenase-1) is a stress-inducible enzyme that plays a protective role in inflammation. Pro-inflammatory mediators, including lipopolysaccharide and cytokines, induce HO-1 expression. The 5′-flanking region of the HO-1 gene contains binding sites for the transcription factors that regulate inflammation, including nuclear factor-κB and activator protein 1. However, these do not appear to mediate lipopolysaccharide-induced HO-1 gene expression. In response to haem and antioxidants, murine HO-1 is regulated by the transcription factor Nrf2 (NF-E2-related factor 2). This transcription factor may also be important in the regulation of HO-1 by pro-inflammatory stimuli.

Upregulated Signaling Pathways in Ruptured Human Saccular Intracranial Aneurysm Wall: An Emerging Regulative Role of Toll-Like Receptor Signaling and Nuclear Factor-κB, Hypoxia-Inducible Factor-1A, and ETS Transcription Factors

Neurosurgery ◽  
2011 ◽  
Vol 68 (6) ◽  
pp. 1667-1676 ◽  
Author(s):  
Mitja I. Kurki ◽  
Sanna-Kaisa Häkkinen ◽  
Juhana Frösen ◽  
Riikka Tulamo ◽  
Mikael von und zu Fraunberg ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Intracranial Aneurysm ◽  
Signaling Pathways ◽  
Binding Sites ◽  
Hypoxia Inducible Factor ◽  
Transcription Factor Binding Sites ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Factor Binding

Abstract BACKGROUND: Aneurysmal subarachnoid hemorrhage, almost always from saccular intracranial aneurysm (sIA), is a devastating form of stroke that affects the working-age population. Cellular and molecular mechanisms predisposing to the rupture of the sIA wall are largely unknown. This knowledge would facilitate the design of novel diagnostic tools and therapies for the sIA disease. OBJECTIVE: To investigate gene expression patterns distinguishing ruptured and unruptured sIA. METHODS: We compared the whole-genome expression profile of 11 ruptured sIA wall samples with that of 8 unruptured ones using oligonucleotide microarrays. Signaling pathways enriched in the ruptured sIA walls were identified with bioinformatic analyses. Their transcriptional control was predicted in silico by seeking the enrichment of conserved transcription factor binding sites in the promoter regions of differentially expressed genes. RESULTS: Overall, 686 genes were significantly upregulated and 740 were downregulated in the ruptured sIA walls. Significantly upregulated biological processes included response to turbulent blood flow, chemotaxis, leukocyte migration, oxidative stress, vascular remodeling; and extracellular matrix degradation. Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factor binding sites were significantly enriched among the upregulated genes. CONCLUSION: We identified pathways and candidate genes associated with the rupture of human sIA wall. Our results may provide clues to the molecular mechanism in sIA wall rupture and insight for novel therapeutic strategies to prevent rupture.

scholarly journals Regulation of IκBβ Expression in Testis

2002 ◽  
Vol 13 (12) ◽  
pp. 4179-4194 ◽  
Author(s):  
Lucy M. Budde ◽  
Chun Wu ◽  
Christopher Tilman ◽  
Iris Douglas ◽  
Sankar Ghosh
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Reporter Gene ◽  
Binding Sites ◽  
Potential Role ◽  
Nuclear Factor Κb ◽  
Transient Transfection ◽  
Nuclear Factor ◽  
Transcription Factor Family ◽  
Novel Target

IκBα and IκBβ are regulators of the nuclear factor-κB (NF-κB) transcription factor family. Both IκBs bind to the same NF-κB dimers and are widely expressed in different cells and tissues. To better understand how these two IκB isoforms differ biologically, we have characterized the expression of IκBβ in testis, a tissue in which IκBα is only minimally expressed. We have found that IκBβ expression is localized within the haploid spermatid stages of spermatogenesis and follows the expression of nuclear NF-κB. IκBβ expression in haploid spermatids is likely regulated by Sox family proteins, members of which are also expressed within spermatids. We have shown that both SRY and Sox-5 can bind to multiple Sox binding sites found within the IκBβ promoter and can enhance transcription of a reporter gene in transient transfection assays. We also demonstrate that IκBβ mRNA is strongly expressed in developing male gonads. These results therefore suggest that IκBβ may be a novel target for transcription factors of the HMG-box SRY/Sox family and imply a potential role for NF-κB/IκBβ in spermatogenesis.

Understanding life and death decisions in human leukaemias

2014 ◽  
Vol 42 (4) ◽  
pp. 747-751
Author(s):  
David J. MacEwan ◽  
Lawrence N. Barrera ◽  
Sujitra Keadsanti ◽  
Stuart A. Rushworth ◽  
Niraj M. Shah ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Apoptotic Cell ◽  
Chemotherapy Resistance ◽  
Nuclear Factor Κb ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cellular Processes ◽  
Cell Death Mechanisms ◽  
Factor Α ◽  
Human Leukaemia

Human leukaemia cells have an often unique ability to either undergo apoptotic cell death mechanisms or, at other times, undergo proliferative expansion, sometimes to the same stimulus such as the pluripotent cytokine TNFα (tumour necrosis factor α). This potential for life/death switching helps us to understand the molecular signalling machinery that underlies these cellular processes. Furthermore, looking at the involvement of these switching signalling pathways that may be aberrant in leukaemia informs us of their importance in cancer tumorigenesis and how they may be targeted pharmacologically to treat various types of human leukaemias. Furthermore, these important pathways may play a crucial role in acquired chemotherapy resistance and should be studied further to overcome in the clinic many drug-resistant forms of blood cancers. In the present article, we uncover the relationship that exists in human leukaemia life/death switching between the anti-apoptotic pro-inflammatory transcription factor NF-κB (nuclear factor κB) and the cytoprotective antioxidant-responsive transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2). We also discuss recent findings that reveal a major role for Btk (Bruton's tyrosine kinase) in both lymphocytic and myeloid forms of human leukaemias and lymphomas.

scholarly journals The Protective Effects of Flavonoids in Cataract Formation through the Activation of Nrf2 and the Inhibition of MMP-9

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3651
Author(s):  
Aaron Hilliard ◽  
Patricia Mendonca ◽  
Tanya D. Russell ◽  
Karam F. A. Soliman
Keyword(s):  
Oxidative Stress ◽  
Redox Homeostasis ◽  
Nuclear Factor Κb ◽  
Protective Role ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Cataract Formation ◽  
Contributing Factors ◽  
Cataract Development

Cataracts account for over half of global blindness. Cataracts formations occur mainly due to aging and to the direct insults of oxidative stress and inflammation to the eye lens. The nuclear factor-erythroid-2-related factor 2 (Nrf2), a transcriptional factor for cell cytoprotection, is known as the master regulator of redox homeostasis. Nrf2 regulates nearly 600 genes involved in cellular protection against contributing factors of oxidative stress, including aging, disease, and inflammation. Nrf2 was reported to disrupt the oxidative stress that activates Nuclear factor-κB (NFκB) and proinflammatory cytokines. One of these cytokines is matrix metalloproteinase 9 (MMP-9), which participates in the decomposition of lens epithelial cells (LECs) extracellular matrix and has been correlated with cataract development. Thus, during inflammatory processes, MMP production may be attenuated by the Nrf2 pathway or by the Nrf2 inhibition of NFκB pathway activation. Moreover, plant-based polyphenols have garnered attention due to their presumed safety and efficacy, nutritional, and antioxidant effects. Polyphenol compounds can activate Nrf2 and inhibit MMP-9. Therefore, this review focuses on discussing Nrf2’s role in oxidative stress and cataract formation, epigenetic effect in Nrf2 activity, and the association between Nrf2 and MMP-9 in cataract development. Moreover, we describe the protective role of flavonoids in cataract formation, targeting Nrf2 activation and MMP-9 synthesis inhibition as potential molecular targets in preventing cataracts.

Anti-inflammatory Actions of Glucocorticoids: Molecular Mechanisms

1998 ◽  
Vol 94 (6) ◽  
pp. 557-572 ◽  
Author(s):  
Peter J. Barnes
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Glucocorticoid Receptors ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Inflammatory Genes ◽  
Anti Inflammatory

1. Glucocorticoids are widely used for the suppression of inflammation in chronic inflammatory diseases such as asthma, rheumatoid arthritis, inflammatory bowel disease and autoimmune diseases, all of which are associated with increased expression of inflammatory genes. The molecular mechanisms involved in this antiinflammatory action of glucocorticoids is discussed, particularly in asthma, which accounts for the highest clinical use of these agents. 2. Glucocorticoids bind to glucocorticoid receptors in the cytoplasm which then dimerize and translocate to the nucleus, where they bind to glucocorticoid response elements (GRE) on glucocorticoid-responsive genes, resulting in increased transcription. Glucocorticoids may increase the transcription of genes coding for antiinflammatory proteins, including lipocortin-1, interleukin-10, interleukin-1 receptor antagonist and neutral endopeptidase, but this is unlikely to account for all of the widespread anti-inflammatory actions of glucocorticoids. 3. The most striking effect of glucocorticoids is to inhibit the expression of multiple inflammatory genes (cytokines, enzymes, receptors and adhesion molecules). This cannot be due to a direct interaction between glucocorticoid receptors and GRE, as these binding sites are absent from the promoter regions of most inflammatory genes. It is more likely to be due to a direct inhibitory interaction between activated glucocorticoid receptors and activated transcription factors, such as nuclear factor-κB and activator protein-1, which regulate the inflammatory gene expression. 4. It is increasingly recognized that glucocorticoids change the chromatin structure. Glucocorticoid receptors also interact with CREB-binding protein (CBP), which acts as a co-activator of transcription, binding several other transcription factors that compete for binding sites on this molecule. Increased transcription is associated with uncoiling of DNA wound around histone and this is secondary to acetylation of the histone residues by the enzymic action of CBP. Glucocorticoids may lead to deacetylation of histone, resulting in tighter coiling of DNA and reduced access of transcription factors to their binding sites, thereby suppressing gene expression. 5. Rarely patients with chronic inflammatory diseases fail to respond to glucocorticoids, although endocrine function of steroids is preserved. This may be due to excessive formation of activator protein-1 at the inflammatory site, which consumes activated glucocorticoid receptors so that they are not available for suppressing inflammatory genes. 6. This new understanding of glucocorticoid mechanisms may lead to the development of novel steroids with less risk of side effects (which are due to the endocrine and metabolic actions of steroids). ‘Dissociated’ steroids which are more active in transrepression (interaction with transcription factors) than transactivation (GRE binding) have now been developed. Some of the transcription factors that are inhibited by glucocorticoid, such as nuclear factor-κB, are also targets for novel anti-inflammatory therapies.

scholarly journals Astaxanthin as a Modulator of Nrf2, NF-κB, and Their Crosstalk: Molecular Mechanisms and Possible Clinical Applications

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 502
Author(s):  
Sergio Davinelli ◽  
Luciano Saso ◽  
Floriana D’Angeli ◽  
Vittorio Calabrese ◽  
Mariano Intrieri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Nuclear Factor Κb ◽  
Protective Role ◽  
Related Factor ◽  
Nuclear Factor ◽  
Molecular Features ◽  
Wide Range ◽  
Pharmaceutical Industries

Astaxanthin (AST) is a dietary xanthophyll predominantly found in marine organisms and seafood. Due to its unique molecular features, AST has an excellent antioxidant activity with a wide range of applications in the nutraceutical and pharmaceutical industries. In the past decade, mounting evidence has suggested a protective role for AST against a wide range of diseases where oxidative stress and inflammation participate in a self-perpetuating cycle. Here, we review the underlying molecular mechanisms by which AST regulates two relevant redox-sensitive transcription factors, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB). Nrf2 is a cellular sensor of electrophilic stress that coordinates the expression of a battery of defensive genes encoding antioxidant proteins and detoxifying enzymes. Likewise, NF-κB acts as a mediator of cellular stress and induces the expression of various pro-inflammatory genes, including those encoding cytokines, chemokines, and adhesion molecules. The effects of AST on the crosstalk between these transcription factors have also been discussed. Besides this, we summarize the current clinical studies elucidating how AST may alleviate the etiopathogenesis of oxidative stress and inflammation.

Overexpression of A1, an NF-κB–Inducible Anti-Apoptotic Bcl Gene, Inhibits Endothelial Cell Activation

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3803-3810 ◽  
Author(s):  
Deborah M. Stroka ◽  
Anne Z. Badrichani ◽  
Fritz H. Bach ◽  
Christiane Ferran
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Cell Activation ◽  
Protective Role ◽  
Nuclear Factor ◽  
Endothelial Cell Activation ◽  
Inflammatory Stimuli ◽  
Inflammatory Proteins ◽  
Transcription Factor Nuclear Factor

Abstract A1 is an anti-apoptotic bcl gene that is expressed in endothelial cells (EC) in response to pro-inflammatory stimuli. We show that in addition to protecting EC from apoptosis, A1 inhibits EC activation and its associated expression of pro-inflammatory proteins by inhibiting the transcription factor nuclear factor (NF)-κB. This new anti-inflammatory function gives a broader dimension to the protective role of A1 in EC. We also show that activation of NF-κB is essential for the expression of A1. Taken together, our data suggest that A1 downregulates not only the pro-apoptotic and pro-inflammatory response, but also its own expression, thus restoring a quiescent phenotype to EC.

Overexpression of A1, an NF-κB–Inducible Anti-Apoptotic Bcl Gene, Inhibits Endothelial Cell Activation

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3803-3810 ◽  
Author(s):  
Deborah M. Stroka ◽  
Anne Z. Badrichani ◽  
Fritz H. Bach ◽  
Christiane Ferran
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Cell Activation ◽  
Protective Role ◽  
Nuclear Factor ◽  
Endothelial Cell Activation ◽  
Inflammatory Stimuli ◽  
Inflammatory Proteins ◽  
Transcription Factor Nuclear Factor

A1 is an anti-apoptotic bcl gene that is expressed in endothelial cells (EC) in response to pro-inflammatory stimuli. We show that in addition to protecting EC from apoptosis, A1 inhibits EC activation and its associated expression of pro-inflammatory proteins by inhibiting the transcription factor nuclear factor (NF)-κB. This new anti-inflammatory function gives a broader dimension to the protective role of A1 in EC. We also show that activation of NF-κB is essential for the expression of A1. Taken together, our data suggest that A1 downregulates not only the pro-apoptotic and pro-inflammatory response, but also its own expression, thus restoring a quiescent phenotype to EC.

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