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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 -
Biochemistry and Biophysics Reports Mar 2016The importance of HS in biology and medicine has been widely recognized in recent years, and protein sulfhydration is proposed to mediate the direct actions of HS...
The importance of HS in biology and medicine has been widely recognized in recent years, and protein sulfhydration is proposed to mediate the direct actions of HS bioactivity in the body. Thioredoxin 1 (Trx1) is an important reducing enzyme that cleaves disulfides in proteins and acts as an -denitrosylase. The regulation of Trx1 on protein -sulfhydration is unclear. Here we showed that Trx1 facilitates protein -desulfhydration. Overexpression of Trx1 attenuated the basal level and HS-induced protein -sulfhydration by direct interaction with -sulfhydrated proteins, i.e., glyceraldehyde 3-phosphate dehydrogenase and pyruvate carboxylase. In contrast, knockdown of Trx1 mRNA expression by short interfering RNA or blockage of Trx1 redox activity with PX12 or 2,4-dinitrochlorobenzene enhanced protein -sulfhydration. Mutation of cysteine-32 but not cysteine-35 in the Trp-Cys-Gly-Pro-Cys motif eliminated the binding of Trx1 with -sulfhydrated proteins and abolished the -desulfhydrating effect of Trx1. All these data suggest that Trx1 acts as an -desulfhydrase.
PubMed: 28955804
DOI: 10.1016/j.bbrep.2015.11.012 -
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 -
Archives of Toxicology Aug 2023MiRNAs are non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Although allergic contact dermatitis has been studied extensively,...
MiRNAs are non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Although allergic contact dermatitis has been studied extensively, few studies addressed miRNA expression and their role in dendritic cell activation. The main aim of this work was to investigate the role of miRNAs in the underlying mechanism of dendritic cell maturation induced by contact sensitizers of different potency. Experiments were conducted using THP-1-derived immature DCs (iDCs). Contact allergens of different potency were used: p-benzoquinone, Bandrowski's base, and 2,4-dinitrochlorobenzene as extreme; nickel sulfate hexahydrate, diethyl maleate and 2-mercaptobenzothiazole as moderate; and α-hexyl cinnamaldehyde, eugenol, and imidazolidinyl urea as weak. Selective inhibitor and mimic miRNAs were then used and several cell surface markers was evaluated as targets. Also, patients patch tested with nickel were analyzed to determine miRNAs expression. Results indicate an important role of miR-24-3p and miR-146a-5p in DCs activation. miR-24-3p was up-regulated by extreme and weak contact allergens, while miR-146a-5p was up-regulated by weak and moderate contact allergens and down-regulated only by the extreme ones. Also, the involvement of PKCβ in contact allergen-induced miR-24-3p and miR-146a-5p expression was demonstrated. Furthermore, the expression of the two miRNAs maintains the same trend of expression in both in vitro and in human conditions after nickel exposure. Results obtained suggest the involvement of miR-24 and miR-146a in DCs maturation process in the proposed in vitro model, supported also by human evidences.
Topics: Humans; Nickel; MicroRNAs; Dermatitis, Allergic Contact; Allergens; Dendritic Cells
PubMed: 37326882
DOI: 10.1007/s00204-023-03542-z -
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 -
Frontiers in Immunology 2024Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal...
BACKGROUND
Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal inflammation and the development and progression of cardiovascular disease and diabetes. However, the anti-inflammatory activity of IMP has not been investigated. This study aimed to elucidate the role of IMP in treating atopic dermatitis (AD).
METHODS
To understand how IMP mediates immunosuppression in AD, IMP was intraperitoneally injected into a extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions mouse model. We also characterized the anti-inflammatory mechanism of IMP by inducing an AD response in keratinocytes through TNF-α/IFN-γ or IL-4 stimulation.
RESULTS
Contrary to the prevailing view that IMP is an unhealthy microbial metabolite, we found that IMP-treated AD-like skin lesions mice showed significant improvement in their clinical symptoms, including ear thickness, epidermal and dermal thickness, and IgE levels. Furthermore, IMP antagonized the expansion of myeloid (neutrophils, macrophages, eosinophils, and mast cells) and Th cells (Th1, Th2, and Th17) in mouse skin and prevented mitochondrial reactive oxygen species production by inhibiting mitochondrial energy production. Interestingly, we found that IMP inhibited AD by reducing glucose uptake in cells to suppress proinflammatory cytokines and chemokines in an AD-like model, sequentially downregulating the PI3K and mTORC2 signaling pathways centered on Akt, and upregulating DDIT4 and AMPK.
DISCUSSION
Our results suggest that IMP exerts anti-inflammatory effects through the metabolic reprogramming of skin inflammation, making it a promising therapeutic candidate for AD and related skin diseases.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Skin; Reactive Oxygen Species; Immunoglobulin E; Anti-Inflammatory Agents; Inflammation; Imidazoles
PubMed: 38533495
DOI: 10.3389/fimmu.2024.1324026 -
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 -
Animal Models and Experimental Medicine Jun 2023Amarogentin (AMA) is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative, anti-inflammatory, and...
BACKGROUND
Amarogentin (AMA) is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative, anti-inflammatory, and antitumor activities. Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by disorders in the regulation of multiple inflammatory cytokines. No effective cure has been found for AD now.
METHODS
We constructed the HaCat and splenocyte model and tested the inhibitory effect of AMA on IL-4, IL-6, and IL-13 secretions using enzyme-linked immunosorbent assay (ELISA). The AD mouse model was constructed and treated with AMA, the severity of skin lesions was observed, epidermal tissue was collected, and epidermal thickness and mast cell infiltration were observed using hematoxylin and eosin and toluidine blue staining, respectively. The expression of kallikrein-related peptidase 7 (KLK7) and filaggrin (FLG) was detected using immunostaining and Western blot analysis. The mRNA expression of KLK7 and FLG was detected using quantitative polymerase chain reaction (qPCR). Blood immunoglobulin E (IgE) secretion was detected.
RESULTS
AMA inhibited IL-6 secreted by tumor necrosis factor (TNF)-α-induced HaCaT cells and reduced IL-4 and IL-13 secreted by phytohemagglutinin (PHA)-induced primary cells in the mice spleen. It was found that the treatment of AMA with 2,4-dinitrochlorobenzene-induced AD-like mice could promote the recovery of dermatitis, reduce the score of dermatitis severity and the scratching frequency, treat the skin lesions, reduce the epidermal thickness, decrease the infiltration of mast cells, reduce the IgE level in serum, decrease the expression levels of AD-related cytokines, increase protein and mRNA expression of FLG, and reduce the protein and mRNA expression of KLK7 in the skin tissues of AD-like mice.
CONCLUSION
In conclusion, AMA inhibits inflammatory response at the cellular level, and AMA reduces the validation response of specific dermatitis mice, relieves pruritus, and repairs the damaged skin barrier.
Topics: Animals; Mice; Humans; Dermatitis, Atopic; Dinitrochlorobenzene; Interleukin-13; Interleukin-6; HaCaT Cells; Interleukin-4; Cytokines; Tumor Necrosis Factor-alpha; Anti-Inflammatory Agents; Immunoglobulin E; RNA, Messenger
PubMed: 36131559
DOI: 10.1002/ame2.12260