scholarly journals Mutant Glucocorticoid Receptor Binding Elements on the Interleukin-6 Promoter Regulate Dexamethasone Effects

2020 ◽  
Author(s):  
Wen-Teng Chang ◽  
Ming-Yuan Hong ◽  
Chien-Liang Chen ◽  
Chi-Yuan Hwang ◽  
Cheng-Chieh Tsai ◽  
...  
Keyword(s):  
Binding Sites ◽  
Inflammatory Process ◽  
Inflammatory Diseases ◽  
Inducible Promoter ◽  
Transcriptional Factor ◽  
Factor Binding ◽  
Inflammatory Processes ◽  
Nuclear Receptor Family ◽  
Receptor Family ◽  
Pro Inflammatory Cytokines

Abstract BackgroundGlucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines. ResultsFive putative GR binding sites and other transcriptional factor binding sites were identified on the interleukin (IL)-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, NF-κB, AP-1, and Sp1-2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The first and third GR binding sites (GR2 and GR3) were noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation. ConclusionsWe concluded that selective GR2 and GR3 modulators might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.

scholarly journals Mutant glucocorticoid receptor binding elements on the interleukin-6 promoter regulate dexamethasone effects

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wen-Teng Chang ◽  
Ming-Yuan Hong ◽  
Chien-Liang Chen ◽  
Chi-Yuan Hwang ◽  
Cheng-Chieh Tsai ◽  
...  
Keyword(s):  
Binding Sites ◽  
Inflammatory Diseases ◽  
Inducible Promoter ◽  
Transcriptional Factor ◽  
Factor Binding ◽  
Inflammatory Processes ◽  
Nuclear Receptor Family ◽  
Specificity Protein ◽  
Receptor Family ◽  
Pro Inflammatory Cytokines

Abstract Background Glucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines, such as interleukin (IL)-6. Results Five putative GR binding sites and other transcriptional factor binding sites were identified on theIL-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, nuclear factor-kappa B (NF-κB), activator protein (AP)-1, and specificity protein (Sp)1–2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The second GR binding site (GR2) was noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation. Conclusions We concluded that selective GR2 modulator might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.

scholarly journals Mutant glucocorticoid receptor binding elements on Interleukin-6 promoter regulate dexamethasone effects

2020 ◽  
Author(s):  
Wen-Teng Chang ◽  
Ming-Yuan Hong ◽  
Chien-Liang Chen ◽  
Cheng-Chieh Tsai ◽  
Chi-Yuan Hwang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucocorticoid Receptor ◽  
Nuclear Receptors ◽  
Inflammatory Cytokines ◽  
Binding Sites ◽  
Inflammatory Process ◽  
Inducible Promoter ◽  
Combined Effects ◽  
The Family ◽  
Pro Inflammatory Cytokines

AbstractGlucocorticoid has been widely used as an important modulator for clinical infectious and inflammatory disease. Glucocorticoid receptor (GR) is a transcription factor belonging to the family of nuclear receptors, regulated anti-inflammatory process and the release of pro-inflammatory cytokines. Five putative GR and other transcription factor binding sites on interleukin (IL)-6 promoter were identified and dexamethasone could reduce LPS-induced IL-6 release. Among them, the mutant transcriptional factors NF-κB, AP-1, and Sp1-2 site decreased the basal and effects of lipopolysaccharide (LPS)-induced IL-6 promoter activities in different responses. GR2/3 seemed to be an important role in both basal and inducible promoter activities in LPS-induced inflammation. We concluded that the selective GR2/3 modulators may have agonistic and antagonistic combined effects and activate important signaling pathway during LPS-stimulated inflammatory process.

Sequence Characterization of S100A8 Gene Reveals Structural Differences of Protein and Transcriptional Factor Binding Sites in Water Buffalo and Yak

2011 ◽  
Vol 22 (3) ◽  
pp. 124-132
Author(s):  
P. Kathiravan ◽  
S. Goyal ◽  
R. S. Kataria ◽  
B. P. Mishra ◽  
S. Jayakumar ◽  
...  
Keyword(s):  
Binding Sites ◽  
Water Buffalo ◽  
Transcriptional Factor ◽  
Sequence Characterization ◽  
Factor Binding ◽  
Structural Differences

scholarly journals The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases

2018 ◽  
Vol 19 (12) ◽  
pp. 3851 ◽  
Author(s):  
Drew Neavin ◽  
Duan Liu ◽  
Balmiki Ray ◽  
Richard Weinshilboum
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Nuclear Receptor ◽  
Binding Sites ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Dependent Manner ◽  
Nucleotide Polymorphisms ◽  
Aryl Hydrocarbon ◽  
Inflammatory Processes ◽  
Targeted Gene Expression

The aryl hydrocarbon receptor (AHR) is a nuclear receptor that modulates the response to environmental stimuli. It was recognized historically for its role in toxicology but, in recent decades, it has been increasingly recognized as an important modulator of disease—especially for its role in modulating immune and inflammatory responses. AHR has been implicated in many diseases that are driven by immune/inflammatory processes, including major depressive disorder, multiple sclerosis, rheumatoid arthritis, asthma, and allergic responses, among others. The mechanisms by which AHR has been suggested to impact immune/inflammatory diseases include targeted gene expression and altered immune differentiation. It has been suggested that single nucleotide polymorphisms (SNPs) that are near AHR-regulated genes may contribute to AHR-dependent disease mechanisms/pathways. Further, we have found that SNPs that are outside of nuclear receptor binding sites (i.e., outside of AHR response elements (AHREs)) may contribute to AHR-dependent gene regulation in a SNP- and ligand-dependent manner. This review will discuss the evidence and mechanisms of AHR contributions to immune/inflammatory diseases and will consider the possibility that SNPs that are outside of AHR binding sites might contribute to AHR ligand-dependent inter-individual variation in disease pathophysiology and response to pharmacotherapeutics.

scholarly journals VEGFA rSNPs, transcriptional factor binding sites and human disease

2013 ◽  
Vol 64 (1) ◽  
pp. 73-76 ◽  
Author(s):  
Norman E. Buroker
Keyword(s):  
Binding Sites ◽  
Human Disease ◽  
Transcriptional Factor ◽  
Factor Binding

scholarly journals VEGFA SNPs and transcriptional factor binding sites associated with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau

2013 ◽  
Vol 63 (3) ◽  
pp. 183-193 ◽  
Author(s):  
Norman E. Buroker ◽  
Xue-Han Ning ◽  
Zhao-Nian Zhou ◽  
Kui Li ◽  
Wei-Jun Cen ◽  
...  
Keyword(s):  
Tibetan Plateau ◽  
High Altitude ◽  
Binding Sites ◽  
Transcriptional Factor ◽  
Altitude Sickness ◽  
Factor Binding

scholarly journals Mechanisms of benzydamine action against local inflammatory process

2019 ◽  
pp. 78-86 ◽  
Author(s):  
G. V. Poryadin ◽  
J. M. Salmasi ◽  
A. N. Kazimirsky
Keyword(s):  
Immune System ◽  
Inflammatory Process ◽  
Inflammatory Diseases ◽  
Local Therapy ◽  
Mechanisms Of Action ◽  
Pharmacological Effects ◽  
Inflammatory Processes ◽  
Antimicrobic Activity ◽  
Acute And Chronic Inflammation ◽  
Inflammatory Action

Local inflammatory diseases caused by various infections are one of the most common pathologies in medical practice. For example, tonsillopharyngitis. This disease is extremely frequent for a physician’s practice. There is a fair amount of drugs, which supposed to be helpful against tonsillopharyngitis, but different drugs are also not the same in their pharmacological effects. In gynecological practice, frequent diseases are specific and non-specific vulvovaginitis, which have inflammatory and infectious components. For administrating local pharmacotherapy in gynecology against inflammation, a large number of drugs with different mechanisms of action are proposed. In this study, we focused on key pathological mechanisms associated with acute and chronic inflammation, for which these drugs should be exposed by their pharmacokinetic and pharmacodynamic properties. The best combination of these properties is available for benzydamine hydrochloride. Benzydamine hydrochloride has a wide antimicrobic activity against bacteria and Candida spices both albicans and non-albicans strains and allows to influence on etiologic cause of the disease. Also benzydamine hydrochloride associated with «cytokine» mechanism of anti-inflammatory action, which means that he does not affect COX enzymes and it allows to avoid gastrotoxic adverse events. Also, in this work showed and discussed aspects of the interaction of benzydamine with local immune system and justification of useful usage the benzydamine for local therapy of acute and chronic inflammatory processes caused by various infections.

Sign in / Sign up

Export Citation Format

Share Document