scholarly journals Role of Aryl Hydrocarbon Receptor Activation in Inflammatory Chronic Skin Diseases

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3559
Author(s):  
Maddalena Napolitano ◽  
Gabriella Fabbrocini ◽  
Fabrizio Martora ◽  
Vincenzo Picone ◽  
Paola Morelli ◽  
...  

Aryl Hydrocarbon Receptor (AhR) is an evolutionary transcription factor which acts as a crucial sensor of different exogenous and endogenous molecules Recent data indicate that AhR is implicated in several physiological processes such as cell physiology, host defense, proliferation and differentiation of immune cells, and detoxification. Moreover, AhR involvement has been reported in the development and maintenance of several pathological conditions. In recent years, an increasing number of studies have accumulated highlighting the regulatory role of AhR in the physiology of the skin. However, there is evidence of both beneficial and harmful effects of AHR signaling. At present, most of the evidence concerns inflammatory skin diseases, in particular atopic dermatitis, psoriasis, acne, and hidradenitis suppurativa. This review examines the role of AhR in skin homeostasis and the therapeutic implication of its pharmacological modulation in these cutaneous inflammatory diseases.

2020 ◽  
Vol 9 (9) ◽  
pp. 3047
Author(s):  
Sara Cacciapuoti ◽  
Maria Luciano ◽  
Matteo Megna ◽  
Maria Annunziata ◽  
Maddalena Napolitano ◽  
...  

The benefits of thermal water in different diseases have been known since ancient times. Over the past decades, a re-assessment of the use of mineral water for the treatment of several pathologic conditions has taken place around the world. Today, water therapy is being practiced in many countries that have a variety of mineral springs considerably different in their hydrogeologic origin, temperature, and chemical composition. Thermal water and balneotherapy offer several advantages: this approach needs no chemicals or potentially harmful drugs; there are almost no side effects during and after treatment, and there is a low risk to the patient’s general health and well-being. However, it is difficult to evaluate the efficacy of this therapeutic approach in clinical practice due to the complexity of molecular mechanisms underlying its efficacy. Here we review the current knowledge of the chemical, immunological, and microbiological basis for therapeutic effects of thermal water with a specific focus on chronic inflammatory skin diseases. We also describe recent evidence of the major dermatologic diseases that are frequently treated by balneotherapy with a remarkable rate of success. Moreover, we discuss the potential role of balneotherapy either alone or as a complement to conventional medical treatments.


Nephron ◽  
2017 ◽  
Vol 137 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jessyca S. Brito ◽  
Natália A. Borges ◽  
Marta Esgalhado ◽  
D''Angelo C. Magliano ◽  
Christophe O. Soulage ◽  
...  

2021 ◽  
Vol 22 (14) ◽  
pp. 7501
Author(s):  
Giorgia Cardinali ◽  
Enrica Flori ◽  
Arianna Mastrofrancesco ◽  
Sarah Mosca ◽  
Monica Ottaviani ◽  
...  

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor expressed in all skin cell types, plays a key role in physiological and pathological processes. Several studies have shown that this receptor is involved in the prevention of inflammatory skin diseases, e.g., psoriasis, atopic dermatitis, representing a potential therapeutic target. We tested the safety profile and the biological activity of NPD-0614-13 and NPD-0614-24, two new synthetic AhR ligands structurally related to the natural agonist FICZ, known to be effective in psoriasis. NPD-0614-13 and NPD-0614-24 did not alter per se the physiological functions of the different skin cell populations involved in the pathogenesis of inflammatory skin diseases. In human primary keratinocytes stimulated with tumor necrosis factor-α or lipopolysaccharide the compounds were able to counteract the altered proliferation and to dampen inflammatory signaling by reducing the activation of p38MAPK, c-Jun, NF-kBp65, and the release of cytokines. Furthermore, the molecules were tested for their beneficial effects in human epidermal and full-thickness reconstituted skin models of psoriasis. NPD-0614-13 and NPD-0614-24 recovered the psoriasis skin phenotype exerting pro-differentiating activity and reducing the expression of pro-inflammatory cytokines and antimicrobial peptides. These data provide a rationale for considering NPD-0614-13 and NPD-0614-24 in the management of psoriasis.


2014 ◽  
Vol 23 (4) ◽  
pp. 278-281 ◽  
Author(s):  
Hye One Kim ◽  
Jin Hye Kim ◽  
Bo Young Chung ◽  
Min Gyu Choi ◽  
Chun Wook Park

2021 ◽  
Vol 22 (9) ◽  
pp. 4983
Author(s):  
Robert Gironés Petit ◽  
Amanda Cano ◽  
Alba Ortiz ◽  
Marta Espina ◽  
Josefina Prat ◽  
...  

Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.


2017 ◽  
Author(s):  
Linda Nocchi ◽  
Mariangela D’Attilia ◽  
Nainika Roy ◽  
Rahul Dhandapani ◽  
Andrei Traista ◽  
...  

AbstractItch is a major symptom of many chronic skin diseases that can exacerbate inflammation by provoking excessive scratching and causing skin damage. Here we develop a novel technology to control itch through molecular guided delivery of a phototoxic agent and near infrared (IR) illumination of the skin. Exploiting the selective binding of the pruritogen Interleukin-31 to itch sensing cells, we generate an engineered IL31SNAPligand derivative (IL31K138A-SNAP) that binds to cells but does not evoke signaling or provoke scratching when injected in vivo. Conjugation of IL31K138A-SNAPto the photosensitizer IRDye®700DX phthalocyanine (IR700) and injection of the skin results in long-term reversal of scratching behavior evoked by IL31 upon near IR illumination. We further develop a topical preparation of IL31K138A-SNAP-IR700 that strikingly, reverses behavioral and dermatological indicators in mouse models of Atopic Dermatitis (AD) and the genetic skin disease Familial Primary Localized Cutaneous Amyloidosis (FPLCA). We demonstrate that this therapeutic effect results from selective retraction of itch sensing neurons in the skin, breaking the cycle of itch and disruption of the skin’s barrier function. Thus, molecule guided photoablation is a powerful new technology for controlling itch and treating inflammatory skin diseases.


2018 ◽  
Vol 115 (6) ◽  
pp. E1319-E1328 ◽  
Author(s):  
Ghjuvan’Ghjacumu Shackleford ◽  
Nirmal Kumar Sampathkumar ◽  
Mehdi Hichor ◽  
Laure Weill ◽  
Delphine Meffre ◽  
...  

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in xenobiotic metabolism. Plexiform neurofibromas (PNFs) can transform into malignant peripheral nerve sheath tumors (MPNSTs) that are resistant to existing therapies. These tumors are primarily composed of Schwann cells. In addition to neurofibromatosis type 1 (NF1) gene inactivation, further genetic lesions are required for malignant transformation. We have quantified the mRNA expression levels of AHR and its associated genes in 38 human samples. We report that AHR and the biosynthetic enzymes of its endogenous ligand are overexpressed in human biopsies of PNFs and MPNSTs. We also detect a strong nuclear AHR staining in MPNSTs. The inhibition of AHR by siRNA or antagonists, CH-223191 and trimethoxyflavone, induces apoptosis in human MPNST cells. Since AHR dysregulation is observed in these tumors, we investigate AHR involvement in Schwann cell physiology. Hence, we studied the role of AHR in myelin structure and myelin gene regulation in Ahr−/− mice during myelin development. AHR ablation leads to locomotion defects and provokes thinner myelin sheaths around the axons. We observe a dysregulation of myelin gene expression and myelin developmental markers in Ahr−/− mice. Interestingly, AHR does not directly bind to myelin gene promoters. The inhibition of AHR in vitro and in vivo increased β-catenin levels and stimulated the binding of β-catenin on myelin gene promoters. Taken together, our findings reveal an endogenous role of AHR in peripheral myelination and in peripheral nerve sheath tumors. Finally, we suggest a potential therapeutic approach by targeting AHR in nerve tumors.


1998 ◽  
Vol 14 (3) ◽  
pp. 226-233 ◽  
Author(s):  
Jürgen Hoyer ◽  
Mechthild Averbeck ◽  
Thomas Heidenreich ◽  
Ulrich Stangier ◽  
Karin Pöhlmann ◽  
...  

Epstein's “Constructive Thinking Inventory” (CTI) was developed to measure the construct of experiential intelligence, which is based on his cognitive-experiential self-theory. Inventory items were generated by sampling naturally occurring automatic cognitions. Using principal component analysis, the findings showed a global factor of coping ability as well as six main factors: Emotional Coping, Behavioral Coping, Categorical Thinking, Personal Superstitious Thinking, Esoteric Thinking, and Naive Optimism. We tested the replicability of this factor structure and the amount of statistical independence (nonredundancy) between these factors in an initial study of German students (Study 1, N = 439) and in a second study of patients with chronic skin disorders (Study 2, N = 187). Factor congruence with the original (American) data was determined using a formula proposed by Schneewind and Cattell (1970) . Our findings show satisfactory factor congruence and statistical independence for Emotional Coping and Esoteric Thinking in both studies, while full replicability or independence could not be found in both for the other factors. Implications for the use and further development of the CTI are discussed.


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