scholarly journals Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis

2020 ◽  
Vol 21 (15) ◽  
pp. 5382 ◽  
Author(s):  
Masutaka Furue
Keyword(s):  
Atopic Dermatitis ◽  
Coal Tar ◽  
Related Factor ◽  
Nuclear Factor ◽  
Signal Transducer ◽  
Barrier Dysfunction ◽  
Beneficial Effects ◽  
Aryl Hydrocarbon ◽  
Transcription Factor Nuclear Factor ◽  
Pruritic Skin

Atopic dermatitis (AD) is an eczematous, pruritic skin disorder with extensive barrier dysfunction and elevated interleukin (IL)-4 and IL-13 signatures. The barrier dysfunction correlates with the downregulation of barrier-related molecules such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL). IL-4 and IL-13 potently inhibit the expression of these molecules by activating signal transducer and activator of transcription (STAT)6 and STAT3. In addition to IL-4 and IL-13, IL-22 and IL-17A are probably involved in the barrier dysfunction by inhibiting the expression of these barrier-related molecules. In contrast, natural or medicinal ligands for aryl hydrocarbon receptor (AHR) are potent upregulators of FLG, LOR, and IVL expression. As IL-4, IL-13, IL-22, and IL-17A are all capable of inducing oxidative stress, antioxidative AHR agonists such as coal tar, glyteer, and tapinarof exert particular therapeutic efficacy for AD. These antioxidative AHR ligands are known to activate an antioxidative transcription factor, nuclear factor E2-related factor 2 (NRF2). This article focuses on the mechanisms by which FLG, LOR, and IVL expression is regulated by IL-4, IL-13, IL-22, and IL-17A. The author also summarizes how AHR and NRF2 dual activators exert their beneficial effects in the treatment of AD.

scholarly journals Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2

Nutrients ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 223 ◽  
Author(s):  
Masutaka Furue ◽  
Hiroshi Uchi ◽  
Chikage Mitoma ◽  
Akiko Hashimoto-Hachiya ◽  
Takahito Chiba ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptors ◽  
Related Factor ◽  
Nuclear Factor ◽  
Healthy Skin ◽  
Aryl Hydrocarbon

Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury

2019 ◽  
Vol 97 (4) ◽  
pp. 287-292 ◽  
Author(s):  
Branislav Kura ◽  
Ashim K. Bagchi ◽  
Pawan K. Singal ◽  
Miroslav Barancik ◽  
Tyler W. LeBaron ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Hydrogen ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cellular Functions ◽  
Artificial System ◽  
Beneficial Effects ◽  
Rat Hearts ◽  
Pre Treatment

Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stresses that impair cellular functions and have been regarded as causative common denominators of many pathological processes. In this review, we report on the beneficial effects of molecular hydrogen in scavenging radicals in an artificial system of•OH formation. As a proof of principle, we also demonstrate that in rat hearts in vivo, administration of molecular hydrogen led to a significant increase in superoxide dismutase as well as pAKT, a cell survival signaling molecule. Irradiation of the rats caused a significant increase in lipid peroxidation, which was mitigated by pre-treatment of the animals with molecular hydrogen. The nuclear factor erythroid 2-related factor 2 is regarded as an important regulator of oxyradical homeostasis, as well as it supports the functional integrity of cells, particularly under conditions of oxidative stress. We suggest that the beneficial effects of molecular hydrogen may be through the activation of nuclear factor erythroid 2-related factor 2 pathway that promotes innate antioxidants and reduction of apoptosis, as well as inflammation.

scholarly journals The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic

2015 ◽  
Vol 43 (4) ◽  
pp. 687-689 ◽  
Author(s):  
Maria A. O’Connell ◽  
John D. Hayes
Keyword(s):  
Small Molecules ◽  
Glycogen Synthase ◽  
Antioxidant Response ◽  
Research Area ◽  
Glycogen Synthase Kinase 3 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Ubiquitin Protein Ligase ◽  
Health And Disease ◽  
Transcription Factor Nuclear Factor

The transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, with gene called NFE2L2) is a master regulator of the antioxidant response. In the last decade, interest has intensified in this research area as its importance in several physiological and pathological processes has become widely recognized; these include redox signalling and redox homoeostasis, drug metabolism and disposition, intermediary metabolism, cellular adaptation to stress, chemoprevention and chemoresistance, toxicity, inflammation, neurodegeneration, lipogenesis and aging. Regulation of Nrf2 is complex and although much attention has focussed on its repression by Kelch-like ECH-associated protein-1 (Keap1), recently it has become increasingly apparent that it is also controlled by cross-talk with other signalling pathways including the glycogen synthase kinase-3 (GSK-3)−β-transducin repeat-containing protein (β-TrCP) axis, ERAD (endoplasmic reticulum-associated degradation)-associated E3 ubiquitin-protein ligase (Hrd1, also called synoviolin), nuclear factor-kappa B (NF-κB), Notch and AMP kinase. Due to its beneficial role in several diseases, Nrf2 has become a major therapeutic target, with novel natural, synthetic and targeted small molecules currently under investigation to modulate the pathway and in clinical trials.

Thyroid hormone in the frontier of cell protection, survival and functional recovery

2015 ◽  
Vol 17 ◽  
Author(s):  
Luis A. Videla ◽  
Virginia Fernández ◽  
Pamela Cornejo ◽  
Romina Vargas ◽  
Iván Castillo
Keyword(s):  
Thyroid Hormone ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Bipolar Disorders ◽  
Nuclear Factor Κb ◽  
Ros Generation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cell Protection ◽  
Beneficial Effects

Thyroid hormone (TH) exerts important actions on cellular energy metabolism, accelerating O2consumption with consequent reactive oxygen species (ROS) generation and redox signalling affording cell protection, a response that is contributed by redox-independent mechanisms. These processes underlie genomic and non-genomic pathways, which are integrated and exhibit hierarchical organisation. ROS production led to the activation of the redox-sensitive transcription factors nuclear factor-κB, signal transducer and activator of transcription 3, activating protein 1 and nuclear factor erythroid 2-related factor 2, promoting cell protection and survival by TH. These features involve enhancement in the homeostatic potential including antioxidant, antiapoptotic, antiinflammatory and cell proliferation responses, besides higher detoxification capabilities and energy supply through AMP-activated protein kinase upregulation. The above aspects constitute the molecular basis for TH-induced preconditioning of the liver that exerts protection against ischemia-reperfusion injury, a strategy also observed in extrahepatic organs of experimental animals and with other types of injury, which awaits application in the clinical setting. Noteworthy, re-adjusting TH to normal levels results in several beneficial effects; for example, it lengthens the cold storage time of organs for transplantation from brain-dead donors; allows a superior neurological outcome in infants of <28 weeks of gestation; reduces the cognitive side-effects of lithium and improves electroconvulsive therapy in patients with bipolar disorders.

scholarly journals Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis

2020 ◽  
Vol 9 (11) ◽  
pp. 3741
Author(s):  
Masutaka Furue
Keyword(s):  
Atopic Dermatitis ◽  
Barrier Function ◽  
Coal Tar ◽  
Calcineurin Inhibitors ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Interleukin 4 ◽  
Skin Barrier Function ◽  
Barrier Dysfunction ◽  
Therapeutic Implications

Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction, and chronic pruritus. As the anti-interleukin-4 (IL-4) receptor α antibody dupilumab improves all three cardinal features of AD, the type 2 cytokines IL-4 and especially IL-13 have been indicated to have pathogenic significance in AD. Accumulating evidence has shown that the skin barrier function is regulated via competition between the aryl hydrocarbon receptor (AHR) axis (up-regulation of barrier) and the IL-13/IL-4‒JAK‒STAT6/STAT3 axis (down-regulation of barrier). This latter axis also induces oxidative stress, which exacerbates inflammation. Conventional and recently developed agents for treating AD such as steroid, calcineurin inhibitors, cyclosporine, dupilumab, and JAK inhibitors inhibit the IL-13/IL-4‒JAK‒STAT6/STAT3 axis, while older remedies such as coal tar and glyteer are antioxidative AHR agonists. In this article, I summarize the pathogenic and therapeutic implications of the IL-13/IL-4‒JAK‒STAT6/STAT3 axis and the AHR axis in AD.

scholarly journals Beneficial effects of Oltipraz, nuclear factor - erythroid – 2 - related factor 2 (Nrf2), on renal damage in unilateral ureteral obstruction rat model

2018 ◽  
Vol 44 (6) ◽  
pp. 1243-1251 ◽  
Author(s):  
Emre Can Polat ◽  
Huseyin Besiroglu ◽  
Levent Ozcan ◽  
Alper Otunctemur ◽  
Ahmet Tugrul Eruyar ◽  
...  
Keyword(s):  
Rat Model ◽  
Ureteral Obstruction ◽  
Renal Damage ◽  
Unilateral Ureteral Obstruction ◽  
Related Factor ◽  
Nuclear Factor ◽  
Beneficial Effects
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