scholarly journals Anti-Inflammatory and Pro-Differentiating Properties of the Aryl Hydrocarbon Receptor Ligands NPD-0614-13 and NPD-0614-24: Potential Therapeutic Benefits in Psoriasis

2021 ◽  
Vol 22 (14) ◽  
pp. 7501
Author(s):  
Giorgia Cardinali ◽  
Enrica Flori ◽  
Arianna Mastrofrancesco ◽  
Sarah Mosca ◽  
Monica Ottaviani ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Skin Diseases ◽  
Cell Types ◽  
Inflammatory Skin Diseases ◽  
Beneficial Effects ◽  
Aryl Hydrocarbon ◽  
Skin Cell ◽  
Therapeutic Benefits ◽  
Inflammatory Skin ◽  
Factor Α

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.

scholarly journals Increased expression of the aryl hydrocarbon receptor in patients with chronic inflammatory skin diseases

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

scholarly journals Stem Cells-Derived Extracellular Vesicles: Potential Therapeutics for Wound Healing in Chronic Inflammatory Skin Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 3130
Author(s):  
Enzo Manchon ◽  
Nell Hirt ◽  
Jean-David Bouaziz ◽  
Nabila Jabrane-Ferrat ◽  
Reem Al-Daccak
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Skin Diseases ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Parental Cell ◽  
Inflammatory Skin Diseases ◽  
Beneficial Effects ◽  
Cell Source ◽  
Inflammatory Skin

Endosome-derived small extracellular vesicles (EVs), often referred to as exosomes, are produced by almost all, if not all, cell types, and are critical for intercellular communication. They are composed of a lipid bilayer associated with membrane proteins and contain a payload of lipids, proteins and regulatory RNAs that depends on the parental cell physiological condition. By transferring their “cargo”, exosomes can modulate the phenotype of neighboring and distant cells. Stem cells (SC) were widely studied for therapeutic applications regarding their regenerative/reparative potential as well as their immunomodulatory properties. Whether from autologous or allogeneic source, SC beneficial effects in terms of repair and regeneration are largely attributed to their paracrine signaling notably through secreted EVs. Subsequently, SC-derived EVs have been investigated for the treatment of various diseases, including inflammatory skin disorders, and are today fast-track cell-free tools for regenerative/reparative strategies. Yet, their clinical application is still facing considerable challenges, including production and isolation procedures, and optimal cell source. Within the emerging concept of “allogeneic-driven benefit” for SC-based therapies, the use of EVs from allogeneic sources becomes the pragmatic choice although a universal allogeneic cell source is still needed. As a unique temporary organ that ensures the mutual coexistence of two allogeneic organisms, mother and fetus, the human placenta offers a persuasive allogeneic stem cell source for development of therapeutic EVs. Advancing cell-free therapeutics nurtures great hope and provides new perspectives for the development of safe and effective treatment in regenerative/reparative medicine and beyond. We will outline the current state of the art in regard of EVs, summarize their therapeutic potential in the context of skin inflammatory disorders, and discuss their translational advantages and hurdles.

Anti-tumor necrosis factor-α therapies for immune-mediated and inflammatory skin diseases

2011 ◽  
Vol 72 (7) ◽  
pp. 615-622
Author(s):  
Clio Dessinioti ◽  
Alexander J. Stratigos ◽  
Andreas Katsambas ◽  
Christina Antoniou
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Skin Diseases ◽  
Inflammatory Skin Diseases ◽  
Immune Mediated ◽  
Inflammatory Skin ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory Skin Disorders

2020 ◽  
Vol 21 (23) ◽  
pp. 8960
Author(s):  
Ji-Eun Chang ◽  
Min Sik Choi
Keyword(s):  
Skin Diseases ◽  
Skin Disorders ◽  
Cytokine Network ◽  
Inflammatory Skin Diseases ◽  
Beneficial Effects ◽  
Wide Range ◽  
Potential Benefits ◽  
Inflammatory Skin ◽  
Allergic Contact ◽  
Hyperglycemic Effect

Due to its anti-hyperglycemic effect, metformin is the first-line medication for the treatment of type 2 diabetes, particularly in people who are obese. However, metformin is a drug with a very wide range of pharmacological properties and reports of its therapeutic effect on diseases including inflammation and cancer are increasing. Numerous research groups have reported that metformin has beneficial effects on a variety of inflammatory skin disorders including psoriasis, acanthosis nigricans, acne, hidradenitis suppurativa, and allergic contact dermatitis. According to these reports, in addition to the well-known action of metformin, that is, its anti-hyperglycemic effect, NF-kB inhibition and the resulting alteration to the cytokine network may be the potential targets of metformin. Its anti-hyperandrogenism effect has also been confirmed as the major action of metformin in some inflammatory skin diseases. Moreover, novel regulatory mechanisms, including autophagy and antioxidant processes, have been suggested as promising mechanisms of action for metformin in inflammatory skin disorders.

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 ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Skin Diseases ◽  
Inflammatory Diseases ◽  
Receptor Activation ◽  
Cell Physiology ◽  
Inflammatory Skin Diseases ◽  
Aryl Hydrocarbon ◽  
Chronic Skin ◽  
Chronic Skin Diseases

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.

scholarly journals Crosstalk between keratinocytes and immune cells in inflammatory skin diseases

2021 ◽  
pp. 418-431
Author(s):  
Xinhui Ni ◽  
Yuping Lai
Keyword(s):  
Immune Cells ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Cell Type ◽  
Physical Barrier ◽  
Inflammatory Skin Diseases ◽  
Major Cell Type ◽  
Inflammatory Skin ◽  
Different Cell Types

Cutaneous homeostasis is maintained by dynamic cellular communications between different cell types in the skin through interactions with various mediators, including cytokines, chemokines and antimicrobial peptides/proteins (AMPs). Keratinocytes, as the major cell type of the epidermis, not only form a passive physical barrier, but also actively participate in the pathogenesis of many, if not all, inflammatory skin diseases. Keratinocytes highly interact with immune cells to shape, amplify or regulate inflammatory responses, thus triggering and/or sustaining these inflammatory skin diseases. In this review, crosstalk between keratinocytes and immune cells is summarized, and its contributions to two major inflammatory skin disorders including psoriasis and atopic dermatitis are highlighted.

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