dinitrobenzenes and Skin-Diseases

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder that affects up to 20 % of children and 10 % of adults worldwide; however, the exact molecular mechanisms remain largely unknown.. In this study, we used integrated transcriptomic and metabolomic analyses to study the potential mechanisms of 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like skin lesions.. We found that DNCB induced AD-like skin lesions, including phenotypical and histomorphological alterations and transcriptional and metabolic alterations in mice. A total of 3413 differentially expressed metabolites were detected between DNCB-induced AD-like mice and healthy controls, which includes metabolites in taurine and hypotaurine metabolism, phenylalanine metabolism, biosynthesis of unsaturated fatty acids, tryptophan metabolism, arachidonic acid metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism pathways. Furthermore, the differentially expressed genes associated (DEGs) with these metabolic pathways were analyzed using RNA sequencing (RNA-seq), and we found that the expression of pyrimidine metabolism-associated genes was significantly increased. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the glycolysis/gluconeogenesis, glucagon signaling pathway and pentose phosphate pathway-associated metabolic genes were dramatically altered.. Our results explain the possible mechanism of AD at the gene and metabolite levels and provide potential targets for the development of clinical drugs for AD.

Topics: Animals; Cytokines; Dermatitis, Atopic; Dinitrobenzenes; Dinitrochlorobenzene; Mice; Mice, Inbred BALB C; Pyrimidines; Skin; Skin Diseases; Transcriptome

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction. Sargassum horneri (S. horneri) is a brown alga that has been widely used in traditional medicine of eastern Asian countries. Recent studies proved that a brown alga S. horneri has anti-inflammatory activity. In this study, we investigated the effect of S. horneri ethanol extract (SHE) against AD in 2,4-dinitrobenzene (DNCB) induced AD in NC/Nga mice. We observed that SHE treatment decreased the epidermal thickness and epidermal hyperplasia that had been worsened through DNCB application. Moreover, SHE significantly inhibited the proliferation of mast cells and decreased the expression of IL-13 on CD4⁺ cells prompted by elevated thymic stromal lymphopoietin (TSLP) expression in DNCB-induced AD in mice. We also demonstrated that SHE directly inhibited the expression of keratinocyte-produced TSLP known to exacerbate skin barrier impairment. Especially, the decrease of filaggrin, an integral component of proper skin barrier function through a function in aggregating keratin filaments, observed in DNCB-induced AD mice was significantly improved when treated with SHE. More importantly, we proved that SHE was able to decrease the serum levels of IgG₁ and IgG₂ₐ, two crucial factors of AD, indicating the protective effect of SHE. Taken together, our findings suggest that SHE may protect NC/Nga mice against DNCB-induced AD via promoting skin barrier function.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Dermatitis, Atopic; Dinitrobenzenes; Immunoglobulin G; Interleukin-13; Keratins; Mice; Plant Extracts; Polyphenols; Sargassum; Skin; Skin Diseases

Topics: Adaptor Proteins, Signal Transducing; Animals; Cytokines; Dermatitis, Atopic; Dinitrobenzenes; Dinitrochlorobenzene; Disease Models, Animal; Immunoglobulin E; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Myeloid Differentiation Factor 88; Signal Transduction; Skin; Skin Diseases; Tenebrio; Trypsin

Huang-Lian-Jie-Du Decoction (HLJDD), is a well-known traditional Chinese herbal formula first written in the Tang dynasty. In Chinese medicine practice, HLJDD is commonly prescribed to treat various inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis.. The present study aimed at investigating the therapeutic effect of HLJDD extract (HLJDE) and to elucidate the underlying molecular mechanisms of action in the 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like mice.. Female Balb/c mice were sensitized with DNCB for three days. After sensitization, mice were challenged with DNCB every three days and orally administrated with HLJDE (150, 300 and 600 mg/kg) daily from day 14 to day 29 for consecutive 16 days. At the end of experiment, the clinical AD scores of the mice were calculated to evaluate the therapeutic effect of HLJDE, and serum, ears and dorsal skin of the mice were collected for unravelling molecular mechanisms.. HLJDE significantly reduced the clinical symptoms in the AD-like mice by inhibiting eosinophil and mast cell infiltration, suppressing the production of Th2-associated cytokine (IL-4) and pro-inflammatory cytokines (TNF-α). In addition, HLJDE significantly suppressed the NF-κB and MAPKs pathways. Moreover, HLJDE was able to accentuate filaggrin expression in the skin lesion when compared to the sensitized mouse without treatment.. HLJDE significantly improved the AD-like symptoms on the DNCB-sensitized mice through mitigating the production of inflammatory mediators via suppressing MAPKs and NF-κB pathways. Additionally, the elevated expression of filaggrin in the skin lesion by HLJDE contributes to the recovery of dysfunctional skin barrier on the DNCB-sensitized mice.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Dermatitis, Atopic; Dinitrobenzenes; Drugs, Chinese Herbal; Eosinophils; Female; Inflammation; Mast Cells; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; NF-kappa B; Plant Extracts; Signal Transduction; Skin; Skin Diseases; Tumor Necrosis Factor-alpha

We studied the effects of lavender oil on mast cell-mediated immediate-type allergic reactions in mice and rats. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 in mice by both topical and intradermal application. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by both topical and intradermal application. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) also inhibited concentration-dependently the histamine release from the peritoneal mast cells by compound 48/80 or anti-DNP IgE. Moreover, lavender oil (1:1000, 1:100, 1:10, 1:0) had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-alpha secretion from peritoneal mast cells. These results indicate that lavender oil inhibits immediate-type allergic reactions by inhibition of mast cell degranulation in-vivo and in-vitro.

Topics: Anaphylaxis; Animals; Dinitrobenzenes; Dose-Response Relationship, Drug; Female; Histamine Release; Hypersensitivity, Immediate; Immunoglobulin E; Lavandula; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Oils, Volatile; p-Methoxy-N-methylphenethylamine; Peritoneum; Plant Extracts; Plant Oils; Plants, Medicinal; Rats; Rats, Wistar; Skin Diseases; Tumor Necrosis Factor-alpha

The percutaneous administration of in vitro haptenated epidermal cells (EC) has become established as a procedure to produce contact sensitivity (CS) in experimental animals for routine use. The cells have also been found to elicit a significant delayed-type skin reaction by intradermal test in the animals sensitized by painting the skin with the hapten. The fate of 2,4-dinitrophenylated (DNP) isogeneic epidermal cell suspensions (EC) injected intradermally was investigated histologically in intact or 2,4-dinitrochlorobenzene (DNCB)-sensitized strain 13 guinea pigs to study the role of the cells in CS. DNP-EC were found to proliferate actively in the dermis and formed EC nests with central keratinization and then elicited inflammatory reaction associated with necrosis of the epidermal structures 7 days after injection in the intact animals. DNP-EC injected intradermally into the animals which had received and reacted against DNCB underwent a suppression of EC proliferation. These findings are discussed in relation to the role of the haptenated EC in CS.

Topics: Animals; Dinitrobenzenes; Dinitrochlorobenzene; Epidermis; Guinea Pigs; Haptens; Hypersensitivity, Delayed; Inflammation; Injections, Intradermal; Male; Oxazolone; Skin Diseases