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Scientific Reports May 2020The main factors involved in the pathogenesis of atopic dermatitis (AD) are skin barrier abnormality, allergy/immunology, and pruritus. Considering how oxidative stress...
The main factors involved in the pathogenesis of atopic dermatitis (AD) are skin barrier abnormality, allergy/immunology, and pruritus. Considering how oxidative stress influences these factors, antioxidant agents may be effective candidates in the treatment of AD. To evaluate the effect of Caffeoyl-Pro-His amide (CA-PH), an antioxidant agent, on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like phenotypes in BALB/c mice. Topical sensitization and challenge by DNCB were performed on the dorsal skin of BALB/c mice to induce AD-like cutaneous lesions, phenotypes, and immunologic response. CA-PH was applied topically for 2 weeks to assess its effects on DNCB-induced AD-like phenotypes. As a result, CA-PH relieved DNCB-induced AD-like phenotypes quantified by dermatitis severity score, scratching duration, and trans-epidermal water loss. Histopathological analysis showed that CA-PH decreased epidermal thickening, the number of mast cells, and eosinophil infiltration in dermis. Immunohistochemical staining revealed that CA-PH recovered skin barrier-related proteins: filaggrin, involucrin, and loricrin. As for the immunologic aspects, CA-PH treatment lowered mRNA or protein levels of interleukin (IL)-4, IL-6, IL-17a, IL-1b, IL-31, and IL-33 levels and thymic stromal lymphopoietin (TSLP) levels in cutaneous tissue, reducing the DNCB-induced serum IgE level elevation. In conclusion, topical CA-PH may be a therapeutic option for the treatment of AD.
Topics: Amides; Animals; Antioxidants; Caffeic Acids; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Eosinophils; Female; Filaggrin Proteins; Heme Oxygenase-1; Immunoglobulin E; Interleukins; Intermediate Filament Proteins; Mast Cells; Membrane Proteins; Mice; Mice, Inbred BALB C; Protein Precursors; Pruritus; Skin; Tight Junctions; Thymic Stromal Lymphopoietin
PubMed: 32439906
DOI: 10.1038/s41598-020-65502-2 -
PeerJ 2022Atopic march (AM), a unique characteristic of allergic diseases, refers to the sequential progression of atopic dermatitis (AD) in infants to allergic asthma and...
BACKGROUND
Atopic march (AM), a unique characteristic of allergic diseases, refers to the sequential progression of atopic dermatitis (AD) in infants to allergic asthma and allergic rhinitis in children and young adults, respectively. Although there are several studies on AM, the establishment of an AM murine model to expand our understanding of the underlying mechanism and to identify the potential biomarkers is yet to be achieved. In this study, an improved murine model was established by applying a method to minimize skin irritation in inducing AD, and it was used to perform integrated analyses to discover candidate biomarkers.
METHODS
To induce atopic dermatitis, 2,4-dinitrochlorobenzene (DNCB) was applied to the ear skin once a week, and this was continued for 5 weeks. From the second application of DNCB, (Dp) extract was applied topically 2 days after each DNCB application; this was continued for 4 weeks. Dp sensitization and intranasal challenges were then performed for 4 weeks to develop conditions mimicking AM.
RESULTS
Exacerbated airway inflammation and allergic responses observed in the AM-induced group suggested successful AM development in our model. Two-dimensional gel electrophoresis (2-DE) and mass spectrometry analysis identified 753 candidate proteins from 124 2-DE spots differentially expressed among the experimental groups. Functional analyses, such as Gene Ontology (GO) annotation and protein-protein interaction (PPI) analysis were conducted to investigate the relationship among the candidate proteins. Seventy-two GO terms were significant between the two groups; heat shock protein 8 (Hspa8) was found to be included in six of the top 10 GO terms. Hspa8 scored high on the PPI parameters as well.
CONCLUSION
We established an improved murine model for AM and proposed Hspa8 as a candidate biomarker for AM.
Topics: Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Heat-Shock Proteins; Skin
PubMed: 35462760
DOI: 10.7717/peerj.13247 -
The Journal of Investigative Dermatology Jun 2023
Topics: Humans; Dinitrochlorobenzene; Dermatitis, Contact; Hypersensitivity; TRPA1 Cation Channel
PubMed: 36634816
DOI: 10.1016/j.jid.2022.12.014 -
Molecules (Basel, Switzerland) Apr 2022Atopic dermatitis (eczema) is a condition that makes skin red and itchy. Though common in children, the condition can occur at any age. Atopic dermatitis is persistent...
Atopic dermatitis (eczema) is a condition that makes skin red and itchy. Though common in children, the condition can occur at any age. Atopic dermatitis is persistent (chronic) and tends to recur periodically. It may be accompanied by asthma or hay fever. No cure has been found for eczema. Therefore, it is very important to develop ingredients that aid the prevention and treatment of atopic dermatitis. Cycloheterophyllin is derived from and has antioxidant and anti-inflammatory activities. However, it still is not understood whether cycloheterophyllin is an anti-atopic dermatitis agent. Keratinocytes (HaCaT cells) and BALB/c mice for inducing AD-like cutaneous lesions were used to evaluate the potential of cycloheterophyllin as an anti-atopic dermatitis agent. The release of pro-inflammatory cytokines induced by treatment of TNF-α/IFN-γ was reduced after pretreatment with cycloheterophyllin. The inhibitory effects could be a contribution from the effect of the MAP kinases pathway. Moreover, the symptoms of atopic dermatitis (such as red skin and itching) were attenuated by pretreatment with cycloheterophyllin. Epidermal hyperplasia and mast cell infiltration were decreased in the histological section. Finally, damage to the skin barrier was also found to recover through assessment of transepidermal water loss. Taken together, prenylflavone-cycloheterophyllin from is a potential anti-atopic dermatitis ingredient that can be used in preventing or treating the condition.
Topics: Animals; Anti-Inflammatory Agents; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Eczema; Flavonoids; HaCaT Cells; Humans; Mice; Mice, Inbred BALB C; Skin
PubMed: 35565961
DOI: 10.3390/molecules27092610 -
Chemical Research in Toxicology Dec 2023Hemoglobin (Hb) adducts are widely used in human biomonitoring due to the high abundance of hemoglobin in human blood, its reactivity toward electrophiles, and adducted...
Hemoglobin (Hb) adducts are widely used in human biomonitoring due to the high abundance of hemoglobin in human blood, its reactivity toward electrophiles, and adducted protein stability for up to 120 days. In the present paper, we compared three methods of analysis of hemoglobin adducts: mass spectrometry of derivatized N-terminal Val adducts, mass spectrometry of N-terminal adducted hemoglobin peptides, and limited proteolysis mass spectrometry . Blood from human donors was incubated with a selection of contact allergens and other electrophiles, after which hemoglobin was isolated and subjected to three analysis methods. We found that the FIE method was able to detect and reliably quantify N-terminal adducts of acrylamide, acrylic acid, glycidic acid, and 2,3-epoxypropyl phenyl ether (PGE), but it was less efficient for 2-methyleneglutaronitrile (2-MGN) and failed to detect 1-chloro-2,4-dinitrobenzene (DNCB). By contrast, bottom-up proteomics was able to determine the presence of adducts from all six electrophiles at both the N-terminus and reactive hemoglobin side chains. Limited proteolysis mass spectrometry, studied for four contact allergens (three electrophiles and a metal salt), was able to determine the presence of covalent hemoglobin adducts with one of the three electrophiles (DNCB) and coordination complexation with the nickel salt. Together, these approaches represent complementary tools in the study of the hemoglobin adductome.
Topics: Humans; Dinitrochlorobenzene; Hemoglobins; Mass Spectrometry
PubMed: 37963067
DOI: 10.1021/acs.chemrestox.3c00294 -
Marine Drugs Aug 2023Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common...
Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common clinical treatments provide limited relief and have some side effects. Therefore, there is a need to develop new effective therapies to treat AD. -oxyzoanthamine is a small molecule alkaloid isolated from Formosan zoanthid. Relevant studies have shown that zoanthamine alkaloids have many pharmacological and biological activities, including anti-lymphangiogenic functions. However, there are no studies on the use of -oxyzoanthamine on the skin. In this paper, -oxyzoanthamine has been shown to have potential in the treatment of atopic dermatitis. Through in vitro studies, it was found that -oxyzoanthamine inhibited the expression of cytokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Atopic dermatitis-like skin inflammation was induced in a mouse model using 2,4-dinitrochlorobenzene (DNCB) in vivo. The results showed that -oxyzoanthamine significantly decreased skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly reduced transepidermal water loss (TEWL), erythema, ear thickness, and spleen weight, while also increasing surface skin hydration. These results indicate that -oxyzoanthamine from zoanthid has good potential as an alternative medicine for treating atopic dermatitis or other skin-related inflammatory diseases.
Topics: Adult; Child; Humans; Animals; Mice; Dinitrochlorobenzene; Dermatitis, Atopic; Skin; Pruritus; Keratinocytes
PubMed: 37623728
DOI: 10.3390/md21080447 -
Biomolecules Oct 2021Atopic dermatitis (AD) is caused by multiple factors that trigger chronic skin inflammation, including a defective skin barrier, immune cell activation, and microbial...
Atopic dermatitis (AD) is caused by multiple factors that trigger chronic skin inflammation, including a defective skin barrier, immune cell activation, and microbial exposure. Although melatonin has an excellent biosafety profile and a potential to treat AD, there is limited clinical evidence from controlled trials that support the use of melatonin as an AD treatment. The delivery of melatonin via the transdermal delivery system is also a challenge in designing melatonin-based AD treatments. In this study, we generated melatonin-loaded extracellular vesicle-mimetic nanoparticles (NVs) to improve the transdermal delivery of melatonin and to evaluate their therapeutic potential in AD. The NVs were spherical nanoparticles with an average size of 100 nm, which is the optimal size for the transdermal delivery of drugs. NVs showed anti-inflammatory effects by suppressing the release of TNF-α and β-hexosaminidase in LPS-treated RAW264.7 cells and compound 48/80-treated RBL-2H3 cells, respectively. NVs showed a superior suppressive effect compared to an equivalent concentration of free melatonin. Treating a 2,4-dinitrofluorobenzene (DNCB)-induced AD-like mouse model with NVs improved AD by suppressing local inflammation, mast cell infiltration, and fibrosis. In addition, NVs effectively suppressed serum IgE levels and regulated serum IFN-γ and IL-4 levels. Taken together, these results suggest that NVs are novel and efficient transdermal delivery systems of melatonin and that NVs can be used as a treatment to improve AD.
Topics: Administration, Topical; Animals; Biomimetics; Dermatitis, Atopic; Dinitrochlorobenzene; Extracellular Vesicles; HEK293 Cells; Humans; Melatonin; Mice; Nanoparticles; RAW 264.7 Cells
PubMed: 34680082
DOI: 10.3390/biom11101450 -
International Journal of Molecular... Jan 2022Oral melatonin supplement has been shown to improve dermatitis severity in children with AD, but the mechanism of the effect is unclear, and it is uncertain whether...
Oral melatonin supplement has been shown to improve dermatitis severity in children with AD, but the mechanism of the effect is unclear, and it is uncertain whether melatonin has a direct immunomodulatory effect on the dermatitis. Topical melatonin treatment was applied to DNCB-stimulated Balb/c mice, and gross and pathological skin findings, serum IgE, and cytokine levels in superficial lymph nodes were analyzed. Secretion of chemokines and cell proliferative response after melatonin treatment in human keratinocyte HaCaT cells were also studied. We found that in DNCB-stimulated Balb/c mice, topical melatonin treatment improved gross dermatitis severity, reduced epidermal hyperplasia and lymphocyte infiltration in the skin, and decreased IP-10, CCL27, IL-4, and IL-17 levels in superficial skin-draining lymph nodes. Melatonin also reduced cytokine-induced secretion of AD-related chemokines IP-10 and MCP-1 and decreased IL-4-induced cell proliferation in HaCaT cells. Melatonin seems to have an immunomodulatory effect on AD, with IP-10 as a possible target, and topical melatonin treatment is a potentially useful treatment for patients with AD.
Topics: Administration, Topical; Animals; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Eczema; Female; Immunomodulating Agents; Immunomodulation; Keratinocytes; Male; Melatonin; Mice; Mice, Inbred BALB C; Severity of Illness Index; Skin
PubMed: 35163297
DOI: 10.3390/ijms23031373 -
Acta Pharmacologica Sinica Nov 2020Sphingosine-1-phosphate (S1P) and its receptors have been implicated in functions of Langerhans cells and atopic dermatitis. In this study, we investigated the roles of...
Sphingosine-1-phosphate (S1P) and its receptors have been implicated in functions of Langerhans cells and atopic dermatitis. In this study, we investigated the roles of S1P receptor type 2 (S1P) in a mouse model of atopic dermatitis, which was induced by topical application of 2,4-dinitrochlorobenzene (DNCB) on ventral skin on D0, followed by repeated DNCB challenge on both ears from D7 to D49. Wild-type mice with atopic dermatitis displayed severe inflammation and mast cell accumulation in ear tissues and elevated IgE levels in serum. Furthermore, the mice showed significantly increased sizes of draining lymph nodes, high levels of inflammatory cytokines (IL-4, IL-13, IL-17, and IFN-γ) in the ears and lymph nodes and high levels of chemokines CCL17 and CCL22 in ears. Administration of JTE-013, a selective antagonist of S1P (3 mg/kg, i.p, from D19 to D49) before DNCB challenge significantly suppressed DNCB-induced atopic responses in ears and lymph nodes. JTE-013 administration also significantly decreased the lymph nodes sizes, the levels of inflammatory cytokines (IL-4, IL-13, IL-17, and IFN-γ) in the ears and lymph nodes, and the levels of chemokines CCL17 and CCL22 in ears. Furthermore, the inflammatory responses of atopic dermatitis were greatly ameliorated in S1pr2 gene-deficient mice. As CCL17 and CCL22 are CCR4 ligands, acting as Th2-attracting chemokines, we investigated CCL17 and CCL22 expression in bone marrow-derived dendritic cells (BMDCs) from wild-type and S1pr2 gene-deficient mice. Addition of IL-4 (10 ng/mL) markedly increased the levels of CCL17 and CCL22, but IL-4-induced CCL17 and CCL22 expression was significantly blunted in BMDCs from S1pr2 gene-deficient mice. Furthermore, pretreatment with JTE-013 (1-30 μM) dose-dependently suppressed this induction in BMDCs from wild-type mice. Our results demonstrate that blockage of S1P ameliorates not only DNCB-induced atopic dermatitis symptoms but also Th2 cell-attracting capacity of dendritic cells, suggesting S1P as a potential therapeutic target for atopic dermatitis.
Topics: Animals; Chemokine CCL17; Chemokine CCL22; Dermatitis, Atopic; Dinitrochlorobenzene; Ear; Lymph Nodes; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Pyrazoles; Pyridines; Sphingosine-1-Phosphate Receptors
PubMed: 32457418
DOI: 10.1038/s41401-020-0412-8 -
International Journal of Molecular... May 2019Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased...
Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.
Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Cyclooxygenase 2; Dermatitis, Atopic; Dinitrochlorobenzene; Female; Immunoglobulins; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Nitric Oxide Synthase Type II; Polyunsaturated Alkamides
PubMed: 31137528
DOI: 10.3390/ijms20102490