scholarly journals Piperine Ameliorates Trimellitic Anhydride-Induced Atopic Dermatitis-Like Symptoms by Suppressing Th2-Mediated Immune Responses via Inhibition of STAT6 Phosphorylation

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2186
Author(s):  
Dae Woon Choi ◽  
Sun Young Jung ◽  
Dong-Hwa Shon ◽  
Hee Soon Shin
Keyword(s):  
Atopic Dermatitis ◽  
Immune Responses ◽  
Ex Vivo ◽  
Mrna Level ◽  
Human Keratinocytes ◽  
Trimellitic Anhydride ◽  
Tnf Α ◽  
Ex Vivo Study ◽  
Gata3 Mrna

Atopic dermatitis (AD) is a common inflammatory skin disease predominately related to Type 2 helper T (Th2) immune responses. In this study, we investigated whether piperine is able to improve AD symptoms using a trimellitic anhydride (TMA)-induced AD-like mouse model. Topical treatment with piperine reduced ear swelling (ear thickness and epidermal thickness) induced by TMA exposure. Furthermore, piperine inhibited pro-inflammatory cytokines such as TNF-α and IL-1β in mouse ears, compared with the TMA-induced AD group. In measuring allergic immune responses in draining lymph nodes (dLNs), we found that IL-4 secretion, GATA3 mRNA level, and STAT6 phosphorylation were suppressed by piperine treatment. In an ex vivo study, piperine also inhibited the phosphorylation of STAT6 on the CD4+ T cells isolated from splenocytes of BALB/c mice, and piperine suppressed IL-4-induced CCL26 mRNA expression and STAT6 phosphorylation in human keratinocytes resulting in the inhibition of infiltration of CCR3+ cells into inflammatory lesions. These results demonstrate that piperine could ameliorate AD symptoms through suppression of Th2-mediated immune responses, including the STAT6/GATA3/IL-4 signaling pathway. Therefore, we suggest that piperine is an excellent candidate as an inhibitor of STAT6 and may help to improve AD symptoms.

scholarly journals Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for atopic dermatitis (AD) treatment

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Audrey Baylet ◽  
Raoul Vyumvuhore ◽  
Marine Laclaverie ◽  
Laëtitia Marchand ◽  
Carine Mainzer ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
Topical Therapy ◽  
Human Keratinocytes ◽  
Raman Microspectroscopy ◽  
Interleukin 4 ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Administration Routes

AbstractCurrently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin. The aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4). Transcutaneous penetration was evaluated by ex vivo studies on tape-stripped pig ear skin. ScFv and Ab visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied in vitro using HEK-Blue™ IL-4/IL-13 cells and normal human keratinocytes (NHKs). After 24 h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on the stratum corneum. In addition, the anti-hIL4 scFv showed very efficient and dose-dependent hIL-4 neutralization. Thus, scFv penetrates through to the upper papillary dermis while Ab mostly remains on the surface, the anti-hIL4 scFv also neutralizes its target effectively suggesting its potential use as topical therapy for AD.

scholarly journals Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for Atopic Dermatitis (AD) treatment

2021 ◽  
Author(s):  
Audrey Baylet ◽  
Raoul Vyumvuhore ◽  
Marine Laclaverie ◽  
Laëtitia Marchand ◽  
Carine Mainzer ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
Topical Therapy ◽  
Human Keratinocytes ◽  
Raman Microspectroscopy ◽  
Poly I:C ◽  
Interleukin 4 ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Polycytidylic Acid

SummaryBackgroundCurrently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis (PSO) or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin.ObjectivesThe aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4).MethodsTranscutaneous penetration was evaluated by ex vivo studies on tape-stripped pig ear skin. Antibody visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied using two 2D models. First, embryonic alkaline phosphatase (SEAP) secretion by HEK-Blue™ IL-4/IL-13 cells, proportional to hIL-4 cells stimulation, was quantified by OD 620 nm measurement in presence or absence of an anti-hIL4 scFv or Ab. Then, normal human keratinocytes (NHKs) were stimulated with polyinosinic-polycytidylic acid (poly I:C) +/− hIL-4 and treated with anti-hIL4 scFv. Human Interleukin-8 (hIL-8) concentrations were determined in culture supernatants by ELISA.ResultsAfter 24h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on the stratum corneum. In addition, the anti-hIL4 scFv showed better efficiency compared to Ab, with a neutralization percentage at 200 nM of 68% and 47%, respectively, in the HEK-Blue™ IL-4/IL-13 model. hIL-8 dosage in stimulated NHKs supernatants revealed that addition of scFv induced a dose-dependent hIL-4 neutralization.ConclusionsscFv penetrates through to the upper papillary dermis while Ab remains on the surface. The anti-hIL4 scFv neutralizes its target effectively in two 2D models suggesting its potential use as topical therapy for AD.

scholarly journals Induction of GITRL expression in human keratinocytes by Th2 cytokines and TNF-α: implications for atopic dermatitis

2012 ◽  
Vol 42 (4) ◽  
pp. 550-559 ◽  
Author(s):  
A. M. Byrne ◽  
E. Goleva ◽  
F. Chouiali ◽  
M. H. Kaplan ◽  
Q. A. Hamid ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Human Keratinocytes ◽  
Th2 Cytokines ◽  
Tnf Α

scholarly journals Influence of the Рriorix vaccination on cytokine profile and IgE level in healthy children and patients with atopic dermatitis

2013 ◽  
Vol 10 (3) ◽  
pp. 30-34
Author(s):  
A P Toptygina ◽  
V A Alioshkin
Keyword(s):  
Atopic Dermatitis ◽  
Serum Level ◽  
Immune Responses ◽  
Similar Distribution ◽  
Healthy Children ◽  
Tnf Α ◽  
Ifn Γ ◽  
Group 2 ◽  
Type Response ◽  
Group 1

Background. The aim of the study was to investigate peculiarities of immune responses on the vaccination with Priorix in healthy children and patients with atopic dermatitis. Methods. Thirty five healthy children aged 1-2 years old (Group 1) and 15 children the same age with atopic dermatitis (Group 2) were vaccinated with Priorix. Serum level of IgE was measured by ELISA, and serum concentrations of 7 cytokines: IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were measured by BioPlex technology before vaccination, 7 days, and 30 days after. Serum level of IgE was measured by ELISA. Results. The level of serum IgE relatively decreased or increased on seventh day after vaccination. In a month IgE level returned back. It was found that in group1 51,4% children demonstrated Th1 type response and 48,6% children showed Th2 type response on the vaccination. Similar distribution was obtained in group 2 (53,3% children showed Th1 type response and 46,7% children demonstrated Th2 type). A significant positive correlation was observed between IgE level increasing and Th2 type of immune response. It was shown that 68,6% of children of group 1 and 66,7% of children of group 2 demonstrated after vaccination the superiority of anti-inflammatory IL-10 over pro-inflammatory TNF-α. We suppose that children with atopic dermatitis can be vaccinated with Priorix.

scholarly journals Evaluation of a Virus-like Nanoparticle Porcine Circovirus Type-2 (PCV2) Capsid Protein Fused with the Pig Immunoglobulin Fc Fragment as a Novel Vaccine Candidate against PCV2 in Mice

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1128
Author(s):  
Qingping Luo ◽  
Waqas Ahmed ◽  
Yichen Dai ◽  
Ali Mohsin ◽  
Haifeng Hang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Fusion Protein ◽  
Capsid Protein ◽  
Ex Vivo ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Porcine Circovirus ◽  
Cell Reactivity ◽  
Fc Fragment

Porcine circovirus Type 2 (PCV2) is a primary etiological pathogen of post-weaning multi-systemic wasting syndrome (PMWS). The capsid protein of PCV2 is the crucial immunogenic protein which can induce antibody generation and immune responses. However, there is still a lack of efficient PCV2 vaccines with high immunogenicity. In the current study, we developed a novel engineered PCV2 capsid (∆1-41aa)-pFc fusion protein (PCFP), which comprised a truncated capsid protein of PCV2 and a porcine IgG Fc fragment, fused to the capsid protein of PCV2 at the C-terminus. We found that this novel fusion protein could auto-assemble into virus-like nanoparticles with an estimated mean diameter of 22.6 nm, characterized by transmission electron microscopy. Immunization of BALB/c mice with this fusion protein significantly increased the production levels of anti-PCV2-capsid protein antibody in serum. Besides, the virus-like nanoparticles, PCFP was demonstrated to induce efficient cellular immune responses in mice, as evident by the high specific T cell reactivity to the PCFP fusion protein and the high production of the immune cytokines IFN-γ and IL-10 in an ex vivo re-stimulation system. Collectively, these findings demonstrate that the PCV2 truncated capsid subunit Fc-fusion protein can induce both cellular and humoral immune responses, and it displays great application potential.

A key role for IL-13 signaling via the type 2 IL-4 receptor in experimental atopic dermatitis

2020 ◽  
Vol 5 (44) ◽  
pp. eaaw2938 ◽  
Author(s):  
Almog Bitton ◽  
Shmuel Avlas ◽  
Hadar Reichman ◽  
Michal Itan ◽  
Danielle Karo-Atar ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Allergic Diseases ◽  
Proof Of Concept ◽  
Potential Therapeutic Target ◽  
Tnf Α ◽  
Allergic Skin ◽  
Insight Into

IL-13 and IL-4 are potent mediators of type 2–associated inflammation such as those found in atopic dermatitis (AD). IL-4 shares overlapping biological functions with IL-13, a finding that is mainly explained by their ability to signal via the type 2 IL-4 receptor (R), which is composed of IL-4Rα in association with IL-13Rα1. Nonetheless, the role of the type 2 IL-4R in AD remains to be clearly defined. Induction of two distinct models of experimental AD in Il13ra1−/− mice, which lack the type 2 IL-4R, revealed that dermatitis, including ear and epidermal thickening, was dependent on type 2 IL-4R signaling. Expression of TNF-α was dependent on the type 2 IL-4R, whereas induction of IL-4, IgE, CCL24, and skin eosinophilia was dependent on the type 1 IL-4R. Neutralization of IL-4, IL-13, and TNF-α as well as studies in bone marrow–chimeric mice revealed that dermatitis, TNF-α, CXCL1, and CCL11 expression were exclusively mediated by IL-13 signaling via the type 2 IL-4R expressed by nonhematopoietic cells. Conversely, induction of IL-4, CCL24, and eosinophilia was dependent on IL-4 signaling via the type 1 IL-4R expressed by hematopoietic cells. Last, we pharmacologically targeted IL-13Rα1 and established a proof of concept for therapeutic targeting of this pathway in AD. Our data provide mechanistic insight into the differential roles of IL-4, IL-13, and their receptor components in allergic skin and highlight type 2 IL-4R as a potential therapeutic target in AD and other allergic diseases such as asthma and eosinophilic esophagitis.

scholarly journals The Role of Galectin-9 as Mediator of Atopic Dermatitis: Effect on Keratinocytes

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 947
Author(s):  
Mab P. Corrêa ◽  
Libnah L. Areias ◽  
Rebeca D. Correia-Silva ◽  
Solange C. G. P. D’Ávila ◽  
Andréia M. Leopoldino ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Human Keratinocytes ◽  
Allergic Diseases ◽  
Control Group ◽  
Biological Functions ◽  
Experimental Conditions ◽  
Control Growth ◽  
Tnf Α ◽  
Ifn Γ

Galectin-9 (Gal-9) is a beta-galactoside-binding protein with a variety of biological functions related to immune response. However, in allergic diseases, its mechanism of action is not fully understood. This study evaluates the expression pattern of Gal-9 in patients with atopic dermatitis (AD), in ovalbumin (OVA)-induced experimental atopic dermatitis (AD) in mice, as well as its effect on human keratinocytes. The skin of OVA-immunized BALB/c mice was challenged with drops containing OVA on days 11, 14–18, and 21–24. HaCaT cells were cultured in the following experimental conditions: control (growth medium only) or stimulated with TNF-α/IFN-γ, or IL-4, or IL-17 with or without Gal-9 treatment. AD was characterized by increased levels of Gal-9 in mouse and human skin, especially in the epidermis, and with a marked influx of Gal-9 positive eosinophils and mast cells compared to the control group. Gal-9 showed an immunomodulatory effect on keratinocytes by decreasing the release of IL-6 by IL-4-stimulated keratinocytes or increasing the IL-6 and RANTES levels by IL-17- or TNF-α/IFN-γ-stimulated cells, respectively. Under IL-17, Gal-9 treatment also altered the proliferation rate of cells. Overall, increased levels of Gal-9 in AD skin contribute to the control of inflammatory response and the proliferative process of keratinocytes, suggesting this lectin as a relevant therapeutic target.

scholarly journals Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus–specific type 2 immune responses

2018 ◽  
Vol 141 (3) ◽  
pp. 1144-1147.e5 ◽  
Author(s):  
Stephan Traidl ◽  
Petra Kienlin ◽  
Gabriele Begemann ◽  
Lichen Jing ◽  
David M. Koelle ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Eczema Herpeticum ◽  
History Of ◽  
Simplex Virus

scholarly journals Immunopotentiotor Effect of α-Tocopherol on Cytokine Expression in the Lymphocytes in the Elderly People

2021 ◽  
Vol 3 (2) ◽  
pp. 107-114
Author(s):  
Atifeh Darabi ◽  
◽  
Setareh Haghighat ◽  
Mehdi Mahdavi ◽  
◽  
...  
Keyword(s):  
Immune Responses ◽  
Elderly People ◽  
Internal Control ◽  
Mononuclear Cells ◽  
Mrna Level ◽  
Control Group ◽  
Gene Expressions ◽  
Elderly Individuals ◽  
Tnf Α ◽  
Ifn Γ

Background: Aging is associated with attenuation of immune responses. Studies show that old people are vulnerable to infectious diseases such as influenza. α-Tocopherol as an immunomodulator affects immune responses. In the present study, the effect of α-tocopherol, on lymphocyte responses i.e. interferon-gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), and nuclear factor-κB (NF-κB) in elderly individuals was evaluated. Materials and Methods: Heparinized blood samples were prepared from 10 elderly individuals (n=10, age >80 years) as the experimental group and 10 young individuals (n= 10, 20-40 years) as the control group. The separated Peripheral Blood Mononuclear Cells (PBMCs) of aged and young individuals were used for treatment with 2 μg/mL of α-tocopherol and 2 μg/mL of Purified Protein Derivative (PPD) after 12 and 24 h incubation period. After isolation of total RNA and synthesize of cDNA, the gene expressions of IFN-γ, TNF-α, and NF-κB were evaluated by real-time PCR method. β-Actin gene was considered as the internal control gene. Results: Results showed that treatment with α-tocopherol increased the IFN-γ expression in old and young lymphocyte groups. The mRNA level of NF-κB increased in the PPD group after 12 h in both old and young groups (p <0.05). There were no alterations in TNF-α expression in both groups. Conclusion: It seems that α-tocopherol is effective in the promotion of cytokine responses in old individuals and may be useful as a supplement for improving the immune system of elderly people.

Effect of Lactobacillus strains on thymus and chemokine expression in keratinocytes and development of atopic dermatitis-like symptoms

2018 ◽  
Vol 9 (4) ◽  
pp. 643-652 ◽  
Author(s):  
T. Kawahara ◽  
N. Hanzawa ◽  
M. Sugiyama
Keyword(s):  
Atopic Dermatitis ◽  
Lactobacillus Reuteri ◽  
Human Keratinocytes ◽  
Skin Lesions ◽  
Suppressive Effect ◽  
Water Soluble ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Atopic Skin ◽  
Water Soluble Extract

Lactobacillus strains, a major group of lactic acid bacteria, are representative food microorganisms that have many potential beneficial effects via their interactions with immune and intestinal epithelial cells. However, little is known about the effect of Lactobacillus strains on atopic dermatitis via keratinocytes, which comprise the physical barrier of the skin. In this study, we report that Lactobacillus strains have a significant suppressive effect on tumour necrosis factor (TNF)-α-induced expression and production of thymus and activation-regulated chemokine (TARC), a T helper 2 cell chemokine responsible for atopic dermatitis, in human keratinocytes. An RNA interference study showed that the effect of Lactobacillus reuteri strain Japan Collection of Microorganisms (JCM) 1112, the most suppressive strain, depended on the presence of Toll-like receptor 2 and the induction of A20 (also known as TNF-α-induced protein 3) and cylindromatosis in HaCaT cells. Topical application of a water-soluble extract of homogenised JCM 1112 cells significantly suppressed the development of house dust mite-induced atopic skin lesions and TARC expression at the lesion sites in NC/Nga mice. Our study provides new insights into the use of Lactobacillus strains as suppressive agents against keratinocyte-involved atopic inflammation of the skin.

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