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International Archives of Allergy and... 2024Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin disease characterized by Th2 cell-mediated type 2 inflammation. Emerging evidence indicated that AD...
INTRODUCTION
Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin disease characterized by Th2 cell-mediated type 2 inflammation. Emerging evidence indicated that AD patients exhibit an increased incidence of oral disorders. In the present study, we sought mechanistic insights into how AD affects periodontitis.
METHODS
Onset of AD was induced by 2,4-dinitrochlorobenzene (DNCB). Furthermore, we induced periodontitis (P) in AD mice. The effect of AD in promoting inflammation and bone resorption in gingiva was evaluated. Hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, immunofluorescence assay, and flow cytometry were used to investigate histomorphology and cytology analysis, respectively. RNA sequencing of oral mucosa is used tissues to further understand the dynamic transcriptome changes. 16S rRNA microbial analysis is used to profile oral microbial composition.
RESULTS
Compared to control group, mice in AD group showed inflammatory signatures and infiltration of a proallergic Th2 (Th2A)-like subset in oral mucosa but not periodontitis, as identified by not substantial changes in mucosa swelling, alveolar bone loss, and TRAP+ osteoclasts infiltration. Similarly, more Th2A-like cell infiltration and interleukin-4 levels were significantly elevated in the oral mucosa of DNCB-P mice compared to P mice. More importantly, AD exacerbates periodontitis when periodontitis has occurred and the severity of periodontitis increased with aggravation of dermatitis. Transcriptional analysis revealed that aggravated periodontitis was positively correlated with more macrophage infiltration and abundant CCL3 secreted. AD also altered oral microbiota, indicating the re-organization of extracellular matrix.
CONCLUSIONS
These data provide solid evidence about exacerbation of periodontitis caused by type 2 dermatitis, advancing our understanding in cellular and microbial changes during AD-periodontitis progression.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; RNA, Ribosomal, 16S; Immunoglobulin E; Anti-Inflammatory Agents; Skin; Inflammation; Periodontitis; Mice, Inbred BALB C; Cytokines
PubMed: 37866360
DOI: 10.1159/000533434 -
Cell Stress & Chaperones Nov 2023Molecular chaperones belonging to the heat shock protein 90 (Hsp90) family are implicated in inflammatory processes and described as potential novel therapeutic targets...
Molecular chaperones belonging to the heat shock protein 90 (Hsp90) family are implicated in inflammatory processes and described as potential novel therapeutic targets in autoimmune/inflammatory skin diseases. While the pathological role of circulating Hsp90 has been recently proposed in patients with atopic dermatitis (AD), a chronic inflammatory skin disease characterized by intense itching and recurrent skin lesions, studies aimed at investigating the role of Hsp90 as a potential target of AD therapy have not yet been conducted. Here, the effects of the Hsp90 blocker STA-9090 (Ganetespib) applied systemically or topically were determined in an experimental mouse model of dinitrochlorobenzene (DNCB)-induced AD. Intraperitoneal administration of STA-9090 ameliorated clinical disease severity, histological epidermal thickness, and dermal leukocyte infiltration in AD mice which was associated with reducing the scratching behavior in DNCB-treated animals. Additionally, topically applied STA-9090 led to lowered disease activity in AD mice, reduced serum levels of IgE, and up-regulated filaggrin expression in lesional skin samples. Our observations suggest that Hsp90 may be a promising therapeutic target in atopic dermatitis and potentially other inflammatory or autoimmune dermatoses.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; Immunoglobulin E; Skin; Inflammation; Antineoplastic Agents; Heat-Shock Proteins; Cytokines; Mice, Inbred BALB C
PubMed: 37851180
DOI: 10.1007/s12192-023-01387-0 -
Journal of Ethnopharmacology Jan 2024Polygonum perfoliatum L. (PP) is classified as a heat-clearing and detoxifying agent in traditional Chinese medicine, and is believed to possess therapeutic properties...
ETHNOPHARMACOLOGICAL RELEVANCE
Polygonum perfoliatum L. (PP) is classified as a heat-clearing and detoxifying agent in traditional Chinese medicine, and is believed to possess therapeutic properties for treating eczema, furuncles, and venomous snake bites. Previous studies have demonstrated that PP extract exhibits multiple bioactivities, including antibacterial, anti-inflammatory, antitumor, antioxidation, and antiviral properties. However, no existing studies have evaluated the effects of PP on animal models of atopic dermatitis (AD)-like skin symptoms, which are closely associated with traditional ethnic usage.
AIM OF THE STUDY
In present study, therefore, we aimed to explore the potential anti-atopic effect of Polygonum perfoliatum L. ethanol extract (PPE) in 2,4-Dinitrochlorobenzene (DNCB)-induced dermatitis-like skin lesions.
MATERIALS AND METHODS
For reaching this aim, DNCB-induced mice with AD-like skin inflammation were subjected to topical administration of PPE gels for a period of 21 days, and subsequently, the biological impacts of PPE were evaluated.
RESULTS
PPE gels effectively mitigated AD-like skin symptoms induced by DNCB in mice, as demonstrated by a marked reduction in epidermal thickness and dermatitis severity. Moreover, PPE significantly decreased the production of various cytokines, including TNF-α, IL-6, IL-1β, IL-4, IL-5, IL-13 and IgE, in addition to suppressed the production of key inflammation-related enzymes (iNOS and COX-2) and decreased the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB in AD-like skin samples. Furthermore, PPE treatment inhibited the abnormally elevated CD4+/CD8+ ratio in DNCB-induced AD mice. The results of the skin irritation test revealed that PPE exhibited no adverse toxicity in mice at dose of 10 mg/day.
CONCLUSIONS
PPE exhibits potential as a safe therapeutic agent for atopic dermatitis by efficiently mitigating DNCB-induced atopic symptoms and diminishing inflammation, and does not carry the risk of over-immunosuppression or treatment-associated adverse effects.
Topics: Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; Skin; Polygonum; Ethanol; Cytokines; Inflammation; Skin Diseases; NF-kappa B; Gels; Mice, Inbred BALB C
PubMed: 37827300
DOI: 10.1016/j.jep.2023.117288 -
Food Science & Nutrition Oct 2023(Maxim.) Trautv. has been used for a long time as a folk remedy. According to studies, it possesses anti-inflammatory, antioxidant, and antibacterial properties....
(Maxim.) Trautv. has been used for a long time as a folk remedy. According to studies, it possesses anti-inflammatory, antioxidant, and antibacterial properties. However, its effects on atopic dermatitis (AD) are poorly studied. Thus, we investigated the therapeutic effect of (Maxim.) Trautv. extract (ABE-M) on 2,4-dinitrochlorobenzene (DNCB)-induced AD. For in vitro analysis, keratinocytes cell lines (HaCaT cells) were used. To evaluate the gene and protein expression levels of cytokines and chemokines, TNF-α/IFN-γ-stimulated HaCaT cells were treated with ABE-M. The cells and the supernatant were collected, then gene and protein levels were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay analysis. For in vivo analysis, BALB/c mice (6 weeks) were randomly separated into five groups ( = 5). The mice were applied DNCB and phosphate-buffered saline, dexamethasone (DX) or ABE-M (50, 100, and 200 mg/kg) was orally administrated for 28 days. At the end, ear tissues and blood were collected for histological analysis and evaluation of cytokines and chemokines. In keratinocytes, ABE-M inhibited the protein and mRNA levels of chemokines, and cytokines exposed by TNF-α/IFN-γ. Similarly, the expression of chemokines was suppressed by ABE-M in AD animal model induced by DNCB and the level of pro-inflammatory cytokines was decreased in a dose-dependent manner. Our research indicates that ABE-M could be a candidate material that can be used to improve skin immunity enhancement, health, and beauty.
PubMed: 37823139
DOI: 10.1002/fsn3.3610 -
Nutrition Research and Practice Oct 2023Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating...
BACKGROUND/OBJECTIVES
Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity.
MATERIALS/METHODS
AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells.
RESULTS
Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 µg/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells.
CONCLUSIONS
These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant. Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.
PubMed: 37780223
DOI: 10.4162/nrp.2023.17.5.855 -
Microscopy and Microanalysis : the... Apr 2023Allergic contact dermatitis (ACD) is an occupation-dependent skin disease that afflicts humans with recurrent, non-specific episodes. Telocyte (TC) is a novel...
Allergic contact dermatitis (ACD) is an occupation-dependent skin disease that afflicts humans with recurrent, non-specific episodes. Telocyte (TC) is a novel interstitial cell discovered in recent years and, together with fibroblasts, constitutes the predominant interstitial cell population in the skin. The purpose of this study was to investigate the morphodynamic changes of interstitial cells, especially TCs, in the skin during the development and treatment of ACD by histological and microscopic scientific methods. Hematoxylin-eosin staining, Masson staining, immunohistochemistry (IHC), immunofluorescence (IF), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to track morphodynamic changes in interstitial cells during the development and treatment in the ACD-involved skin induced by 2,4-dinitrochlorobenzene (DNCB). The results demonstrated that TCs were mainly present around dermal collagen fibers, perivascular (except dermal papillary vascular loop), and skin appendages, which expressed CD34+, Vimentin+, PDGFR-α+, and α-SMA-. The absence of TCs during ACD development and after ACD recovery causes dermal interstitial cell dysregulation. The special anatomical relationships between TCs, immune cells, and follicular stem cells were also revealed, suggesting their potential dermatitis-regulating function. In a nutshell, our results provide morphodynamic evidence for the process of ACD development and recovery and offer potential cytological ideas for ACD treatment.
Topics: Humans; Telocytes; Interstitial Cells of Cajal; Skin; Dermatitis, Allergic Contact; Immunohistochemistry
PubMed: 37749732
DOI: 10.1093/micmic/ozad010 -
FASEB Journal : Official Publication of... Oct 2023PYR-41 is an irreversible and cell permeable inhibitor of ubiquitin-activating enzyme E1, and has been reported to inhibit the degradation of IκB protein. Previous...
PYR-41 is an irreversible and cell permeable inhibitor of ubiquitin-activating enzyme E1, and has been reported to inhibit the degradation of IκB protein. Previous studies have shown that PYR-41 has effects on anti-inflammatory, but whether it has therapeutic effects on allergic dermatitis is unclear. The aim of this research was to explore the therapeutic effects of PYR-41 on atopic dermatitis. The effects of PYR-41 on the activation of NF-κB signaling pathway and the expression of inflammatory genes in HaCat cells were tested by western blot and qPCR. A mouse model was built, and the AD-like skin lesions were induced by 2,4-dinitrochlorobenzene (DNCB). Then, the treatment effects of PYR-41 were examined by skin severity score, ear swelling, ELISA, and qPCR. The results showed that PYR-41 can significantly reduce the K63-linked ubiquitination level of nuclear factor-κB essential modulator (NEMO) and tumor necrosis factor receptor associated factor 6 (TRAF6), inhibit the proteasomal degradation of IκBα, thereby activate TNF-α-induced NF-κB signaling pathway in HaCat cells. In addition, DNCB-treated mice have significant reduction in symptoms after treated by PYR-41, including reduced ear thickening and reduced skin damage. Serum tests showed that PYR-41 significantly reduced the expression of IgE, IFN-γ, and TNF-α. In conclusion, the current results suggest that PYR-41 has potential to reduce the symptoms of atopic dermatitis.
Topics: Animals; Mice; Ubiquitin-Activating Enzymes; Dermatitis, Atopic; Dinitrochlorobenzene; Tumor Necrosis Factor-alpha; NF-kappa B; Skin Diseases
PubMed: 37738047
DOI: 10.1096/fj.202200951RRR -
Animal Biotechnology Nov 2024The current study was performed to determine the effect of dietary vitamin E, sesamin and thymoquinone bioactive lignans derived from sesame and black seed on...
Evaluation the effect of dietary vitamin E, sesamin and thymoquinone bioactive compounds on immunological response, intestinal traits and MUC-2 gene expression in broiler Japanese quails ().
The current study was performed to determine the effect of dietary vitamin E, sesamin and thymoquinone bioactive lignans derived from sesame and black seed on immunological response, intestinal traits and Mucin gene expression in broiler quails. Three hundred and fifty (one days-old) quails were allotted to seven dietary treatments with five replicates as an experimental randomized design study. Treatments were basal diet as a control, control +100 and +200 mg of vitamin E, sesamin and thymoquinone per each kg of diet respectively. At 35 d of age, two quails from each pen were chosen, weighted, slaughtered, eviscerated and lymphoid organ relative weights were measured. Anti-body titers against Newcastle disease (ND), Sheep red blood cell (SRBC), and infectious bronchitis virus (IBV) and Avian influenza (AI) vaccination were determined. The serum activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum antioxidant activates such as superoxide dismutase (SOD),glutathione peroxidase(GPX), catalase (CAT) and total antioxidant capacity (TAC) were examined. The cell mediated immunity by dinitrochlorobenzene (DNCB) and phytohemagglutinin (PHA) challenges were assessed. The microflora populations of ileum, morphological traits of jejunum and mucin gene expression were analyzed. Data showed that the lymphoid organ (thymus, spleen and Bursa) relative weights and antibody titer against HI, AI, SRBC and IB vaccination were increased compared to the control ( ≤ 0.05). Serum activities of ALP, ALT and AST were decreased under influences of dietary treatments ( ≤ 0.05). The serum antioxidant activates of GPX,SOD,CAT and TAC were increased and Increasing in mean skin thickness after DNCB challenge and decrease wing web swelling response to PHA mitojen injection were observed ( ≤ 0.05). and colonies were decrease and colonies increased instead ( ≤ 0.05). The villus height and surface, crypt depth and goblet cells density were increased compared to the control ( ≤ 0.05). The expression of MUC gene increased under influnces of vitamin E, sesamin and thymoquinone supplemented diets ( ≤ 0.05).
Topics: Animals; Sheep; Coturnix; Vitamin E; Antioxidants; Dinitrochlorobenzene; Chickens; Diet; Dietary Supplements; Lignans; Superoxide Dismutase; Gene Expression; Mucins; Animal Feed; Dioxoles; Benzoquinones
PubMed: 37729462
DOI: 10.1080/10495398.2023.2259437 -
Food Science of Animal Resources Sep 2023It is known that animal-origin medicine could be one of effective treatment to remedy atopic dermatitis (AD) by controlling the cytokines. Cicadidae Periostracum (CP),...
The Slough of Cicadidae Periostracum Ameliorated Lichenification by Inhibiting Interleukin (IL)-22/Janus Kinase (JAK) 1/Signal Transducer and Activator of Transcription (STAT) 3 Pathway in Atopic Dermatitis.
It is known that animal-origin medicine could be one of effective treatment to remedy atopic dermatitis (AD) by controlling the cytokines. Cicadidae Periostracum (CP), the slough of , has been frequently used for treating AD and skin affliction in traditional Korean Medicine. This study is aimed at investigating the ameliorating effects of CP on AD and its potential mechanism. The dinitrochlorobenzene sensitized mice were treated with CP for 2 weeks. The various biomarkers and the dermatitis scores presented that CP treatment can induce the visual and biological improvements of AD model. Pruritus, the most serious symptom of AD, which can cause repeated scratching behaviors and finally lead to lichenification, was reduced with CP treatment by regulating the inflammatory reactions. In addition, CP treatment diminished the number of mast cells that are known for causing inflammatory reactions. Moreover, it is proven that CP can decline secretion of interleukin-22, which means CP treatment has anti-inflammatory effects. CP treatment can correct the imbalance of helper T (Th)1 and Th2, downregulating thymic stromal lymphopoietin that leads to decrease of mRNA level of inflammatory cytokines. The crucial role of CP treatment is controlling of the Janus kinase 1/signal transducer and activator of transcription 3 pathway. In addition, CP treatment has the inhibitory effects on kallikrein related peptidase (KLK) 5 and KLK7. Taken together, CP treatment can ameliorate most symptoms and problems caused by AD disease, improving the AD patients' life quality.
PubMed: 37701738
DOI: 10.5851/kosfa.2023.e40 -
Journal of Traditional Chinese Medicine... Oct 2023To investigate the efficacy of Zhenxin Anshen formula (, ZXAS) on atopic dermatitis (AD) by transient receptor potential vanilloid 1 (TRPV1) and transient receptor...
Zhenxin Anshen formula ameliorates atopic der-matitis-like skin dysfunction in mice and regulation of transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 in Neural pathways.
OBJECTIVE
To investigate the efficacy of Zhenxin Anshen formula (, ZXAS) on atopic dermatitis (AD) by transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) signalling pathway in mice and .
METHODS
AD-like lesions were induced by 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice. BALB/c mice were divided into five groups: normal control, model control, cetirizine, low-, medium-, and high-dose of ZXAS. After ZXAS in-tervention, the skin lesions and blood samples were collected for hematoxylin and eosin-stained and measuring the concentrations of inflammatory cytokines. Immun-oglobulin E (IgE), interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP) were de-tected by Enzyme-linked immunosorbent assay (ELISA). The spinal cords were collected for measuring the expression of gastrin-releasing peptide receptor (GRPR), TRPV1, and TRPA1 by using immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In addition, 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, ELISA, and Western blotting were conducted for analysis of primary dorsal root ganglia (DRG) neurons .
RESULTS
ZXAS treatment improved DNCB-induced AD-like lesions through reducing dermatitis score, number of scratching and epidermal thickness, accompanied by the de-creased IgE and Th2 inflammatory cytokines. ZXAS also supressed the mRNA and protein expression of GRPR, TRPV1, and TRPA1 in the spinal cord. The medicated sera of ZXAS decreased capsaicin-induced Ca influx and downregulated the expression of TRPV1, TRPA1, and phospholipase C in DRG neurons.
CONCLUSIONS
The therapeutic effect of ZXAS on AD may be related to the regulation of TRPV1 and TRPA1 and inhibition of Ca2+ signals in neurons.
Topics: Animals; Mice; Ankyrins; Dinitrochlorobenzene; Antineoplastic Agents; Dermatitis, Atopic; Cytokines; Neural Pathways; Dinitrobenzenes; Immunoglobulin E
PubMed: 37679976
DOI: 10.19852/j.cnki.jtcm.20230802.003