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European Journal of Immunology Jul 2017Allergic contact dermatitis is a primarily T-cell-mediated inflammatory skin disease induced by exposure to small molecular-weight haptens, which covalently bind to...
Allergic contact dermatitis is a primarily T-cell-mediated inflammatory skin disease induced by exposure to small molecular-weight haptens, which covalently bind to proteins. The abundance of cutaneous T cells that recognize CD1a antigen-presenting molecules raises the possibility that MHC-independent antigen presentation may be relevant in some hapten-driven immune responses. Here we examine the ability of contact sensitizers to influence CD1-restricted immunity. Exposure of human antigen-presenting cells such as monocyte-derived dendritic cells and THP-1 cells to the prototypical contact sensitizer dinitrochlorobenzene potentiated the response of CD1a- and CD1d-autoreactive T cells, which released a vast array of cytokines in a CD1- and TCR-dependent manner. The potentiating effects of dinitrochlorobenzene depended upon newly synthesized CD1 molecules and the presence of endogenous stimulatory lipids. Further examination of a broad panel of contact sensitizers revealed 1,4-benzoquinone, resorcinol, isoeugenol, and cinnamaldehyde to activate the same type of CD1-restricted responses. These findings provide a basis for the antigen-specific activation of skin-associated CD1-restricted T cells by small molecules and may have implications for contact sensitizer-induced inflammatory skin diseases.
Topics: Acrolein; Antigen Presentation; Antigens, CD1; Benzoquinones; Cell Line; Dendritic Cells; Dermatitis, Contact; Dinitrochlorobenzene; Eugenol; Humans; Lipids; Lymphocyte Activation; Monocytes; Natural Killer T-Cells; Resorcinols; Skin; T-Lymphocytes
PubMed: 28440548
DOI: 10.1002/eji.201746939 -
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 -
International Journal of Molecular... Dec 2021The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide....
The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1β, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.
Topics: Animals; Anti-Inflammatory Agents; Chemokines; Dermatitis, Atopic; Dinitrochlorobenzene; Filaggrin Proteins; Immunity; Inflammation; Keratinocytes; Male; Mast Cells; Membrane Proteins; Mice; Plant Extracts; Protein Precursors; Pruritus; Skin; T-Lymphocytes
PubMed: 35008651
DOI: 10.3390/ijms23010226 -
Nutrients Dec 2017has been used for food substances, as well as in herbal medicines for allergic diseases such as asthma. This study aimed to investigate the anti-atopic dermatitis (AD)...
has been used for food substances, as well as in herbal medicines for allergic diseases such as asthma. This study aimed to investigate the anti-atopic dermatitis (AD) effects of the total extract of rhizomes and active fractionson murine oxazolone- and 2,4-dinitrochlorobenzene-induced models of AD. Specific AD symptoms, such as erythema, ear swelling, and epidermis thickening, were significantly reduced in the oxazolone-mediated AD BALB/c mice upon topical application of rhizomes 95% EtOH extract (DQ). DQEA ( rhizomes EtOAc fraction) was beneficial for protecting the skin barrier against AD in DNCB-sensitized SKH-1 hairless mice. Decreased total serum IgE and IL-4 levels could be observed in atopic dorsal skin samples of the DQEA-treated group. On the basis of the phytochemical analysis, DQEA was found to contain dioscin and gracillin as its main compounds. Therapeutic applications with might be useful in the treatment of AD and related inflammatory skin diseases.
Topics: Animals; Cell Line; Dermatitis, Atopic; Dinitrochlorobenzene; Dioscorea; Female; Gene Expression Regulation; Immunoglobulin E; Interleukin-4; Mice; Mice, Hairless; Mice, Inbred BALB C; Oxazolone; Phytotherapy; Plant Extracts; RNA, Messenger; Rats; Rhizome
PubMed: 29206209
DOI: 10.3390/nu9121324 -
International Journal of Molecular... Oct 2021Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has...
Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has anti-inflammatory and anti-aging effects on the skin, but its effect on mast cells has not yet been studied in detail. In this study, we used mast cells (RBL-2H3 cells) and mouse models to study the anti-allergic and inflammatory effects of neferine. First, we found that neferine inhibits the degranulation of mast cells and the expression of cytokines. In addition, we observed that when mast cells were stimulated by A23187/phorbol 12-myristate-13-acetate (PMA), the elevation of intracellular calcium was inhibited by neferine. The phosphorylation of the MAPK/NF-κB pathway is also reduced by pretreatment of neferine. The results of in vivo studies show that neferine can improve the appearance of dermatitis and mast cell infiltration caused by dinitrochlorobenzene (DNCB). Moreover, the expressions of barrier proteins in the skin are also restored. Finally, it was found that neferine can reduce the scratching behavior caused by compound 48/80. Taken together, our results indicate that neferine is a very good anti-allergic and anti-inflammatory natural product. Its effect on mast cells contributes to its pharmacological mechanism.
Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Benzylisoquinolines; Calcimycin; Calcium; Cell Line; Cell Movement; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Mast Cells; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; NF-kappa B; Phosphorylation; Signal Transduction
PubMed: 34681651
DOI: 10.3390/ijms222010994 -
British Medical Journal Apr 1979
Topics: Alopecia Areata; Dinitrochlorobenzene; Female; Humans; Male; Nitrobenzenes
PubMed: 435922
DOI: 10.1136/bmj.1.6169.1017-b -
Biomedical and Environmental Sciences :... Nov 2022The effect of oral cadmium (Cd) intake to influence contact skin allergies was examined, since it is known that Cd is a heavy metal that affects many tissues, including...
OBJECTIVE
The effect of oral cadmium (Cd) intake to influence contact skin allergies was examined, since it is known that Cd is a heavy metal that affects many tissues, including the skin, in which it disturbs homeostasis, thus resulting in inflammation and injury.
METHODS
Male rats were evoked with experimental contact hypersensitivity reaction (CHS) to hapten dinitrochlorobenzene (DNCB), after prolonged (30 day) oral exposure to an environmentally relevant Cd dose (5 ppm). The ear cell population was analyzed with flow cytometry. Cytokine production by ear skin cells and the activity of skin-draining lymph node (DLN) cells were measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS
Orally acquired Cd (5 ppm) increased CHS intensity only in Dark Agouti (DA) rats by affecting inflammatory responses in both the sensitization (an increase of IFN-γ and IL-17 cytokine production) and challenge (an increase of CD8 and CD4 cell number and TNF, IFN-γ and IL-17 cytokine production) phases. An increased CHS reaction was seen in Albino Oxford (AO) rats only at a high Cd dose (50 ppm), during the challenge phase (an increase of CD8 and CD4 cell number and TNF, IFN-γ and IL-17 cytokine production).
CONCLUSION
These novel data indicate that oral Cd intensifies the skin response to sensitizing chemicals such as DNCB.
Topics: Male; Rats; Animals; Allergens; Cadmium; Dinitrochlorobenzene; Interleukin-17; Cytokines
PubMed: 36443256
DOI: 10.3967/bes2022.132 -
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 -
Journal of Immunology (Baltimore, Md. :... Jun 2022Despite the known dangers of contact allergens and their long-lasting use as models in immunology, their molecular mode of action largely remains unknown. In this study,...
Despite the known dangers of contact allergens and their long-lasting use as models in immunology, their molecular mode of action largely remains unknown. In this study, we report that a contact allergen, 1-chloro-2,4-dinitrobenzene (DNCB), elicits contact hypersensitivity through binding the protein we identify. Starting from an unbiased sampling of proteomics, we found nine candidate proteins with unique DNCB-modified peptide fragments. More than half of these fragments belonged to heat shock protein 90 (HSP90), a common stress-response protein and a damage-associated molecular pattern, and showed the highest probability of incidence. Inhibition and short hairpin RNA knockdown of HSP90 in human monocyte cell line THP-1 suppressed the potency of DNCB by >80%. Next, we successfully reduced DNCB-induced contact hypersensitivity in HSP90-knockout mice, which confirmed our findings. Finally, we hypothesized that DNCB-modified HSP90 activates the immune cells through HSP90's receptor, CD91. Pretreatment of CD91 in THP-1 cell lines and BALB/c mice attenuated the potency of DNCB, consistent with the result of HSP90-knockout mice. Altogether, our data show that DNCB-HSP90 binding plays a role in mediating DNCB-induced contact hypersensitivity, and the activation of CD91 by DNCB-modified HSP90 proteins could mediate this process.
Topics: Allergens; Animals; Dermatitis, Contact; Dinitrochlorobenzene; HSP90 Heat-Shock Proteins; Heat-Shock Proteins; Humans; Mice; Mice, Inbred BALB C
PubMed: 35675957
DOI: 10.4049/jimmunol.2101023 -
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