scholarly journals The role of interleukin-24 in atopic dermatitis

2021 ◽  
Author(s):  
Yen Hai Vu ◽  
Masutaka Furue ◽  
Gaku Tsuji
Keyword(s):  
Atopic Dermatitis ◽  
Inflammatory Responses ◽  
Skin Barrier ◽  
Human Keratinocytes ◽  
Barrier Disruption ◽  
Aryl Hydrocarbon ◽  
Receptor Modulator ◽  
Chronic Pruritus

Atopic dermatitis (AD) is characterized by skin barrier disruption, type 2 immune dysregulation, chronic pruritus, and abnormal colonization by Staphylococcus aureus (S. aureus). Tapinarof, an aryl hydrocarbon receptor modulator, has been demonstrated to attenuate the development of AD in clinical studies. Recently, we found that tapinarof upregulated the expression of filaggrin and loricrin, which are essential proteins in skin barrier functions. Paradoxically, tapinarof induced interleukin (IL)-24 secretion by normal human keratinocytes. IL-24 is produced by T helper 2 lymphocytes and keratinocytes following stimulation by type 2 cytokines, and IL-24 is upregulated in the skin of patients with AD. Furthermore, IL-24 contributes to skin barrier disruption and hyperplasia in AD, and it may exacerbate skin inflammatory responses, itch, and S. aureus infection. In this review, we summarized the current findings regarding the detrimental role of IL-24 in AD, thereby suggesting that co-treatment of tapinarof with therapeutics that block IL-24 signaling may represent a promising strategy for managing AD.

scholarly journals Role of AHR Ligands in Skin Homeostasis and Cutaneous Inflammation

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3176
Author(s):  
Nieves Fernández-Gallego ◽  
Francisco Sánchez-Madrid ◽  
Danay Cibrian
Keyword(s):  
Atopic Dermatitis ◽  
Barrier Function ◽  
Inflammatory Responses ◽  
Normal Skin ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
In Vitro Assays ◽  
Skin Barrier Function

Aryl hydrocarbon receptor (AHR) is an important regulator of skin barrier function. It also controls immune-mediated skin responses. The AHR modulates various physiological functions by acting as a sensor that mediates environment–cell interactions, particularly during immune and inflammatory responses. Diverse experimental systems have been used to assess the AHR’s role in skin inflammation, including in vitro assays of keratinocyte stimulation and murine models of psoriasis and atopic dermatitis. Similar approaches have addressed the role of AHR ligands, e.g., TCDD, FICZ, and microbiota-derived metabolites, in skin homeostasis and pathology. Tapinarof is a novel AHR-modulating agent that inhibits skin inflammation and enhances skin barrier function. The topical application of tapinarof is being evaluated in clinical trials to treat psoriasis and atopic dermatitis. In the present review, we summarize the effects of natural and synthetic AHR ligands in keratinocytes and inflammatory cells, and their relevance in normal skin homeostasis and cutaneous inflammatory diseases.

scholarly journals The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

scholarly journals Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3638
Author(s):  
Yoon-Young Sung ◽  
Heung-Joo Yuk ◽  
Won-Kyung Yang ◽  
Seung-Hyung Kim ◽  
Dong-Seon Kim
Keyword(s):  
Atopic Dermatitis ◽  
Immunoglobulin E ◽  
Allergic Inflammation ◽  
Skin Barrier ◽  
Human Keratinocytes ◽  
Skin Lesions ◽  
Protein Levels ◽  
Siraitia Grosvenorii ◽  
Ifn Γ

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.

scholarly journals Functional interactions between Mi-2β and AP1 complexes control response and recovery from skin barrier disruption

2019 ◽  
Vol 217 (3) ◽  
Author(s):  
Sayaka Shibata ◽  
Mariko Kashiwagi ◽  
Bruce A. Morgan ◽  
Katia Georgopoulos
Keyword(s):  
Stress Response ◽  
Transcriptional Response ◽  
Selective Reduction ◽  
Skin Barrier ◽  
Human Keratinocytes ◽  
Chromatin Accessibility ◽  
Stress Signaling ◽  
Genetic Ablation ◽  
Barrier Disruption ◽  
Stress Response Genes

Keratinocytes respond to environmental signals by eliciting induction of genes that preserve skin’s integrity. Here we show that the transcriptional response to stress signaling is supported by short-lived epigenetic changes. Comparison of chromatin accessibility and transcriptional changes induced by barrier disruption or by loss of the nucleosome remodeler Mi-2β identified their striking convergence in mouse and human keratinocytes. Mi-2β directly repressed genes induced by barrier disruption by restricting AP1-enriched promoter-distal sites, occupied by Mi-2β and JUNB at steady state and by c-JUN after Mi-2β depletion or stress signaling. Barrier disruption led to a modest reduction in Mi-2β expression and a further selective reduction of Mi-2β localization at stress response genes, possibly through competition with activated c-JUN. Consistent with a repressive role at stress response genes, genetic ablation of Mi-2β did not prevent reestablishment of barrier integrity but was required for return to homeostasis. Thus, a competition between Mi-2β–repressive and activating AP1 complexes may permit rapid transcriptional response to and resolution from stress signaling.

scholarly journals Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 321 ◽  
Author(s):  
Fabio Seiti Yamada Yoshikawa ◽  
Josenilson Feitosa de Lima ◽  
Maria Notomi Sato ◽  
Yasmin Álefe Leuzzi Ramos ◽  
Valeria Aoki ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Complex Disease ◽  
Skin Barrier ◽  
Inflammatory Skin Disease ◽  
Innate And Adaptive Immunity ◽  
Concise Review ◽  
Intense Pruritus ◽  
Immunological Factors

Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30–100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of S. aureus superantigen-activated signaling pathways, highlighting their involvement in AD pathogenesis, with an emphasis on skin barrier disruption, innate and adaptive immunity dysfunction, and microbiome alterations. A better understanding of the combined mechanisms of AD pathogenesis may enhance the development of future targeted therapies for this complex disease.

Antihistamines in the Treatment of Atopic Dermatitis

2003 ◽  
Vol 7 (6) ◽  
pp. 467-473 ◽  
Author(s):  
Sari M. Herman ◽  
Ronald B. Vender
Keyword(s):  
Atopic Dermatitis ◽  
Medline Search ◽  
Conventional Management ◽  
Search Terms ◽  
Early Evidence ◽  
Cell Release ◽  
Inflammatory Skin Disorder ◽  
Chronic Pruritus ◽  
Enhance Patient Care

Background: Atopic dermatitis (AD) is an inflammatory skin disorder that is exceedingly challenging to treat. A prominent feature of AD is chronic pruritus. Early evidence suggested that pruritus in AD was partially due to mast cell release of histamine. Conversely, recent studies do not validate the role of histamine in the pathogenesis of pruritus. Conventional management continues to include the wide use of antihistamines to treat the persistent itch, however, there is an urgent need for therapy which will reduce the severity of pruritus for these patients. Objective: To review the evidence in the literature for the use of antihistamines in the treatment of atopic dermatitis. Methods: A MEDLINE search (1966–2002) was performed to obtain studies examining the use of antihistamines in the treatment of atopic dermatitis. Search terms included: atopic dermatitis; eczema; antihistamines; azatadine; brompheniramine; cetirizine; chlorpheniramine; clemastine; cyclizine; cyproheptadine; desloratadine; diphenhydramine; fexofenadine; hydroxyzine; loratadine; meclizine; promethazine; trimeprazine. Further references were gathered from these publications. Results: Historically, antihistamines have been used in the treatment of AD. However, this review shows that the evidence for its use is inconclusive. At present, several antihistamines continue to provide relief of pruritus by central sedation, and they can also be used therapeutically for concomitant allergic conditions associated with AD. More clinical trials examining the therapeutic efficacy of antihistamines, especially with the newer nonsedating antihistamines, are necessary to elucidate their role in the treatment of AD. Conclusion: Dermatologists require additional evidence regarding the efficacy of antihistamines and their mechanism of action in the treatment of AD to enhance patient care.

scholarly journals The Plasmatic Aldosterone and C-Reactive Protein Levels, and the Severity of Covid-19: The Dyhor-19 Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2315 ◽  
Author(s):  
Orianne Villard ◽  
David Morquin ◽  
Nicolas Molinari ◽  
Isabelle Raingeard ◽  
Nicolas Nagot ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Clinical Course ◽  
Clinical Status ◽  
Plasma Renin ◽  
Ordinal Scale ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein

Background. The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells. Since the RAAS can induce and modulate pro-inflammatory responses, it could play a key role in the pathophysiology of Covid-19. Thus, we aimed to determine the levels of plasma renin and aldosterone as indicators of RAAS activation in a series of consecutively admitted patients for Covid-19 in our clinic. Methods. Plasma renin and aldosterone levels were measured, among the miscellaneous investigations needed for Covid-19 management, early after admission in our clinic. Disease severity was assessed using a seven-category ordinal scale. Primary outcome of interest was the severity of patients’ clinical courses. Results. Forty-four patients were included. At inclusion, 12 patients had mild clinical status, 25 moderate clinical status and 7 severe clinical status. In univariate analyses, aldosterone and C-reactive protein (CRP) levels at inclusion were significantly higher in patients with severe clinical course as compared to those with mild or moderate course (p < 0.01 and p = 0.03, respectively). In multivariate analyses, only aldosterone and CRP levels remained positively associated with severity. We also observed a positive significant correlation between aldosterone and CRP levels among patients with an aldosterone level greater than 102.5 pmol/L. Conclusions. Both plasmatic aldosterone and CRP levels at inclusion are associated with the clinical course of Covid-19. Our findings may open new perspectives in the understanding of the possible role of RAAS for Covid-19 outcome.

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