scholarly journals Interleukin-31 and Pruritic Skin

2021 ◽  
Vol 10 (9) ◽  
pp. 1906
Author(s):  
Masutaka Furue ◽  
Mihoko Furue
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Skin Inflammation ◽  
Subjective Symptom ◽  
Oncostatin M ◽  
Inflammatory Skin Diseases ◽  
Prurigo Nodularis ◽  
T Helper 2 ◽  
Oncostatin M Receptor ◽  
Pruritic Skin

Skin inflammation often evokes pruritus, which is the major subjective symptom in many inflammatory skin diseases such as atopic dermatitis and prurigo nodularis. Pruritus or itch is a specific sensation found only in the skin. Recent studies have stressed the pivotal role played by interleukin-31 (IL-31) in the sensation of pruritus. IL-31 is produced by various cells including T helper 2 cells, macrophages, dendritic cells and eosinophils. IL-31 signals via a heterodimeric receptor composed of IL-31 receptor A (IL-31RA) and oncostatin M receptor β. Recent clinical trials have shown that the anti-IL-31RA antibody nemolizumab can successfully decrease pruritus in patients with atopic dermatitis and prurigo nodularis. The IL-31 pathway and pruritic skin are highlighted in this review article.

scholarly journals Lack of Endogenous Annexin A1 Increases Mast Cell Activation and Exacerbates Experimental Atopic Dermatitis

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 51 ◽  
Author(s):  
Jéssica Parisi ◽  
Mab Corrêa ◽  
Cristiane Gil
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cell ◽  
Cell Activation ◽  
Skin Diseases ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Mast Cell Activation ◽  
Skin Thickness ◽  
Annexin A1 ◽  
Inflammatory Skin Diseases

Annexin A1 (AnxA1) is a protein with potent anti-inflammatory actions and an interesting target that has been poorly explored in skin inflammation. This work evaluated the lack of endogenous AnxA1 in the progression of ovalbumin (OVA)-induced atopic dermatitis (AD)-like skin lesions. OVA/Alum-immunized C57BL/6 male wild-type (WT) and AnxA1 null (AnxA1-/-) mice were challenged with drops containing OVA on days 11, 14–18 and 21–24. The AnxA1-/- AD group exhibited skin with intense erythema, erosion and dryness associated with increased skin thickness compared to the AD WT group. The lack of endogenous AnxA1 also increased IgE relative to WT animals, demonstrating exacerbation of the allergic response. Histological analysis revealed intense eosinophilia and mast-cell activation in AD animals, especially in AnxA1-/-. Both AD groups increased skin interleukin (IL)-13 levels, while IL-17A was upregulated in AnxA1-/- lymph nodes and mast cells. High levels of phosphorylated ERK were detected in keratinocytes from AD groups. However, phospho-ERK levels were higher in the AnxA1-/- when compared to the respective control groups. Our results suggest AnxA1 as an important therapeutic target for inflammatory skin diseases.

scholarly journals The molecular basis for IL-31 production and IL-31-mediated itch transmission: from biology to drug development

2021 ◽  
Author(s):  
Kazufumi Kunimura ◽  
Yoshinori Fukui
Keyword(s):  
T Cells ◽  
Drug Development ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Oncostatin M ◽  
Helper T Cells ◽  
Inflammatory Skin Diseases ◽  
Itch Sensation ◽  
Oncostatin M Receptor

Abstract Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases in the world. It is characterized by recurrent eczematous lesions and intense itch, and many cytokines are involved in the pathogenesis of AD. Among them, much attention has been paid to interleukin 31 (IL-31) as an AD-associated itch mediator. IL-31 is mainly produced by CD4+ helper T cells and transmits the signals via a heterodimeric receptor composed of IL-31 receptor A (IL-31RA) and oncostatin M receptor (OSMR), both of which are expressed in dorsal root ganglion (DRG) neurons. However, the molecular mechanisms of how IL-31 is produced in helper T cells upon stimulation and transmits the itch sensation to the brain were largely unknown. Recently, by using original mouse models of AD, we have identified endothelial PAS domain 1 (EPAS1) and neurokinin B (NKB) as key molecules critical for IL-31 production and IL-31-mediated itch transmission, respectively. These molecules could be novel drug targets for AD-associated itch. This review highlights our recent findings, which show the functional significance of these molecules in the IL-31-induced itch sensation, referring to their application to drug development.

scholarly journals Caffeoyl-Prolyl-Histidine Amide Inhibits Fyn and Alleviates Atopic Dermatitis-Like Phenotypes via Suppression of NF-κB Activation

2020 ◽  
Vol 21 (19) ◽  
pp. 7160
Author(s):  
Hayan Jeong ◽  
Jee Youn Shin ◽  
Kwanghyun Lee ◽  
Su-Jin Lee ◽  
Hyo-Jin Chong ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Nuclear Factor Kappa B ◽  
Skin Diseases ◽  
Nuclear Translocation ◽  
Mammalian Target Of Rapamycin ◽  
Kinetic Studies ◽  
Skin Inflammation ◽  
Nuclear Factor ◽  
Inflammatory Skin Diseases ◽  
Nuclear Factor Kappa

Caffeic acid (CA) is produced from a variety of plants and has diverse biological functions, including anti-inflammation activity. It has been recently demonstrated that caffeoyl-prolyl-histidine amide (CA-PH), which is CA conjugated with proline-histidine dipeptide, relieves atopic dermatitis (AD)-like phenotypes in mouse. In this study, we investigated the molecular mechanism underlying CA-PH-mediated alleviation of AD-like phenotypes using cell line and AD mouse models. We confirmed that CA-PH suppresses AD-like phenotypes, such as increased epidermal thickening, infiltration of mast cells, and dysregulated gene expression of cytokines. CA-PH suppressed up-regulation of cytokine expression through inhibition of nuclear translocation of NF-κB. Using a CA-PH affinity pull-down assay, we found that CA-PH binds to Fyn. In silico molecular docking and enzyme kinetic studies revealed that CA-PH binds to the ATP binding site and inhibits Fyn competitively with ATP. CA-PH further suppressed spleen tyrosine kinase (SYK)/inhibitor of nuclear factor kappa B kinase (IKK)/inhibitor of nuclear factor kappa B (IκB) signaling, which is required for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. In addition, chronic application of CA-PH, in contrast with that of glucocorticoids, did not induce up-regulation of regulated in development and DNA damage response 1 (REDD1), reduction of mammalian target of rapamycin (mTOR) signaling, or skin atrophy. Thus, our study suggests that CA-PH treatment may help to reduce skin inflammation via down-regulation of NF-κB activation, and Fyn may be a new therapeutic target of inflammatory skin diseases, such as AD.

scholarly journals Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses

2021 ◽  
Vol 22 (4) ◽  
pp. 1553
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Jungmin Jeon ◽  
Yun Hoo Park ◽  
Tae-Cheol Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Immune Responses ◽  
Chromatin Remodeling ◽  
Skin Diseases ◽  
Immunoglobulin E ◽  
Critical Role ◽  
Interleukin 4 ◽  
Inflammatory Skin Diseases ◽  
Immune Disorder

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.

scholarly journals Itch in Atopic Dermatitis – What Is New?

2021 ◽  
Vol 8 ◽  
Author(s):  
Franz J. Legat
Keyword(s):  
Atopic Dermatitis ◽  
Intracellular Signaling ◽  
Sleep Disturbances ◽  
Skin Diseases ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Inflammatory Skin Diseases ◽  
New Era ◽  
Short And Long Term ◽  
Chronic Pruritus

Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.

Deficiency of n-6 polyunsaturated fatty acids is mainly responsible for atopic dermatitis-like pruritic skin inflammation in special diet-fed hairless mice

2013 ◽  
Vol 22 (4) ◽  
pp. 272-277 ◽  
Author(s):  
Masanori Fujii ◽  
Hiroyuki Nakashima ◽  
Junko Tomozawa ◽  
Yuki Shimazaki ◽  
Chie Ohyanagi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Atopic Dermatitis ◽  
Polyunsaturated Fatty Acids ◽  
Skin Inflammation ◽  
Hairless Mice ◽  
Special Diet ◽  
Pruritic Skin

scholarly journals Relationship between Skin Microbiota and Skin Biophysical Parameters in Inflammatory Skin Disease: A Systematic Review

2021 ◽  
Vol 7 (1) ◽  
pp. 1-6
Author(s):  
Paola Perugini ◽  
Keyword(s):  
Systematic Review ◽  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Bacterial Flora ◽  
Skin Microbiota ◽  
Biophysical Parameters ◽  
Microbial Composition ◽  
Inflammatory Skin Diseases ◽  
Starting Point ◽  
Inflammatory Skin

Many recent studies highlight the importance of skin microbiota for skin health. Alterations in the balance of bacterial flora cause the development of inflammatory skin diseases such as acne, atopic dermatitis, or psoriasis. This systematic review aims to investigate the relationship, in these skin diseases, between skin microbiota and skin biophysical parameters, such as pH, Transepidermal Water Loss (TEWL), Hydration (HI) and sebum levels. Google Scholar, Medline via Pubmed, and Web of Science were considered as scientific database to search studies about this topic. Research about acne and psoriasis did not produce any results. For this reason, in this review, only articles concerning atopic dermatitis were discussed. Therefore, a possible correlation between skin barrier functionality and microbial composition was also investigated. So, this could be a starting point for the diagnosis of atopic dermatitis or, more generally, for all inflammatory skin diseases.

scholarly journals Nutritional Factors in the Prevention of Atopic Dermatitis in Children

2021 ◽  
Vol 8 ◽  
Author(s):  
Thulja Trikamjee ◽  
Pasquale Comberiati ◽  
Enza D'Auria ◽  
Diego Peroni ◽  
Gian Vincenzo Zuccotti
Keyword(s):  
Atopic Dermatitis ◽  
Life Stress ◽  
Skin Diseases ◽  
Maternal Diet ◽  
Skin Inflammation ◽  
Future Research ◽  
Skin Barrier Function ◽  
Nutritional Factors ◽  
Nutrition And Diet

Atopic dermatitis is one of the most frequent chronic skin diseases worldwide and often develops within the first few years of life. Recent advancements in our knowledge of its pathophysiology have brought to light the role of genetic predisposition and environmental triggers. With the increasing prevalence of allergic diseases, there is a strong need for a better understanding of the various modifiable eliciting factors of such conditions. The concomitant rise in food allergy and insights into the skin barrier function has highlighted the role of nutrition and diet in the prevention and modification of allergic disorders. Furthermore, the identification of the skin as an important route of sensitization, and the risk of progression to asthma later in life, stress the significance of optimizing our management of skin inflammation in the prevention of allergies. Many nutritional factors, including the type of maternal diet during pregnancy, the duration of breastfeeding, the epicutaneous exposure of allergenic food proteins in the first few years of life, the timing of the introduction of complementary foods, the supplementation of vitamins and probiotics/prebiotics during prenatal and early life, have been assessed as potential targets for the prevention of atopy and eczema. Here, we review the latest data addressing prenatal and perinatal nutritional and dietary interventions in the primary prevention of atopic dermatitis. Also, we define knowledge gaps and targets for future research in the prevention of atopic dermatitis.

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