OBJECTIVE: To investigate the anti-inflammatory potential of Ampelopsis japonica on contact dermatitis (CD). METHODS: A total of 38 Balb/c mice were divided into 5 groups by using a random number table: normal mice (n=6), CD model mice (n=8), CD mice treated with 3 or 30 mg/kg of the ethanol extract of A. japonica (EEAJ, n=8) and 7.5 mg/kg dexamethasone treated CD mice (DEX, n=8). CD was induced using topical application of 1-fluoro-2,4-dinitrofluorobenzene in mice. EEAJ and DEX were topically applied to the shaved skin of each mouse for 6 days, and the effects of EEAJ and DEX on skin lesions and color, histopathological abnormalities such as epidermal hyperplasia and immune cell infiltration, and tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production were investigated. The effects on changes in body weights and spleen/body weight ratio were also investigated. RESULTS: EEAJ at 30 mg/kg significantly prevented scaling, erythema and enlargement of skin weight compared to using carbon dioxide. EEAJ also prevented epithelial hyperplasia and immune cell infiltrations induced by repeated application of DNFB (P<0.01). In addition, EEAJ significantly lowered levels of TNF-α, IL-6 and MCP-1 (P<0.05 or P<0.01). The anti-inflammatory effects of EEAJ were similar to those of DEX. CONCLUSION A. japonica may be a new therapeutic agent with the potential to reduce or replace corticosteroids and its mechanisms are closely related to regulation of TNF-α production.
Ampelopsis ; Animals ; Anti-Inflammatory Agents/therapeutic use* ; Cytokines ; Dermatitis, Contact/pathology* ; Dinitrofluorobenzene/therapeutic use* ; Hyperplasia/drug therapy* ; Interleukin-6 ; Mice ; Mice, Inbred BALB C ; Plant Extracts/therapeutic use* ; Tumor Necrosis Factor-alpha

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
Acetamides ; therapeutic use ; Animals ; Chemokine CXCL10 ; metabolism ; Chloroquine ; toxicity ; Chronic Disease ; Cyclopropanes ; adverse effects ; Dehydration ; complications ; Dinitrofluorobenzene ; adverse effects ; Disease Models, Animal ; Formaldehyde ; toxicity ; Freund's Adjuvant ; toxicity ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; drug effects ; Pain ; chemically induced ; Pruritus ; chemically induced ; pathology ; Pyrimidines ; therapeutic use ; Receptors, CXCR3 ; antagonists & inhibitors ; genetics ; metabolism ; Skin ; pathology ; Spinal Cord ; drug effects ; metabolism ; pathology ; Time Factors ; p-Methoxy-N-methylphenethylamine ; toxicity

Aryl hydrocarbon receptor (AhR) regulates both innate and adaptive immune responses by sensing a variety of small synthetic and natural chemicals, which act as its ligands. AhR, which is expressed in dendritic cells (DCs), regulates the differentiation of DCs. However, effects of AhR on the differentiation of DCs are variable due to the heterogeneity of DCs in cell surface marker expression, anatomical location, and functional responses. The plasmacytoid DCs (pDCs), one of DC subsets, not only induce innate as well as adaptive immune responses by secreting type I interferons and pro-inflammatory cytokines, but also induce IL-10 producing regulatory T cell or anergy or deletion of antigen-specific T cells. We showed here that AhR ligands indoxyl 3-sulfate (I3S) and indole-3-carbinol (I3C) inhibited the development of pDCs derived from bone marrow (BM) precursors induced by FMS-like tyrosine kinase 3 ligand (Flt3L). I3S and I3C downregulated the expression of signal transducer and activator of transcription 3 (STAT3) and E2-2 (Tcf4). In mice orally treated with I3S and I3C, oral tolerance to dinitrofluorobenzene was impaired and the proportion of CD11c⁺B220⁺ cells in mesenteric lymph nodes was reduced. These data demonstrate that AhR negatively regulates the development of pDCs from BM precursors induced by Flt3L, probably via repressing the expression of STAT3.
Animals ; Bone Marrow ; Cell Differentiation ; Cytokines ; Dendritic Cells* ; Dinitrofluorobenzene ; fms-Like Tyrosine Kinase 3* ; Immune Tolerance ; Interferon Type I ; Interleukin-10 ; Ligands* ; Lymph Nodes ; Mice ; Population Characteristics ; Receptors, Aryl Hydrocarbon* ; STAT3 Transcription Factor ; T-Lymphocytes ; Vascular Endothelial Growth Factor Receptor-1*

Bamboo salt (BS) is a traditional Korean food, and has been reported to have anti-cancer, anti-inflammatory, and anti-metastatic effects. However, the anti-atopic dermatitis (AD) activity of BS has not been described yet. In the present study, we examined the preventive effect of BS on AD. The effect of oral administration of BS was tested in a 2, 4-dinitrofluorobenzene (DNFB)-induced AD animal model, by histological analysis, enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, caspase-1 assay, and Western blotting analysis. BS administration reduced the total clinical severity and scratching frequencies, compared with the AD group. In the serum of DNFB-induced AD mice, the levels of IgE, histamine, thymic stromal lymphopoietin (TSLP), interleukin (IL)-5, and IL-13 were significantly reduced by BS treatment. BS significantly reduced the protein and mRNA expression of TSLP, IL-6, and tumor necrosis factor-α in the AD skin lesions. BS markedly reduced the infiltration of inflammatory cells. Furthermore, the activation of caspase-1 was reduced by BS in the AD skin lesions. Our results suggested that BS should be considered as a candidate treatment for allergic inflammatory diseases including AD.
Animals ; Caspase 1 ; genetics ; immunology ; Dermatitis, Atopic ; chemically induced ; drug therapy ; genetics ; immunology ; Dinitrofluorobenzene ; adverse effects ; Disease Models, Animal ; Female ; Histamine ; immunology ; Humans ; Immunoglobulin E ; immunology ; Interleukin-13 ; genetics ; immunology ; Interleukin-5 ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Sodium Chloride, Dietary ; administration & dosage

OBJECTIVETo investigate the therapeutic effect of mustard seed on allergic contact dermatitis (ACD) in mice and explore the mechanism.

METHODSEighteen BALB/c mice were randomly divided into normal control group, model group and mustard seed group. The mice in the normal control group and model group were fed with normal chow, and those in mustard seed group were given 5% mustard seed mixed in the chow. Three weeks later, ACD was induced on the ear using 2, 4-dinitrofluorobenzene. After 24 h, the swelling of the ear was examined, and the rats were sacrificed to collect the ear tissue ears and blood for histopathological and immunohistochemical examinations, RT-PCR and enzyme-linked immunosorbent assay.

RESULTSIn mice with ACD, feeding with mustard seeds significantly lessened the ear swelling, improved the tissue histopathology, lowered the number of infiltrating Langerhans cells, and reduced the expressions of IL-1β, TNF-α and IL-6 mRNA in the ear, but did not cause significant changes in serum levels of IL-4, IFN-γ and IL-17.

CONCLUSIONMustard seed inhibits ACD in mice possibly by suppressing the expressions of IL-1β, TNF-α and IL-6 mRNA and inhibiting Langerhans cell migration in the epidermis.

Animals ; Dermatitis, Allergic Contact ; drug therapy ; metabolism ; Dinitrofluorobenzene ; adverse effects ; Female ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mustard Plant ; Seeds ; Tumor Necrosis Factor-alpha ; metabolism

Animals ; Dinitrofluorobenzene ; Ear ; Electrons ; Erbium ; Gene Expression ; Humans ; Inflammation ; Interleukin-1beta ; Laser Therapy ; Lymphocytes ; Male ; Mice ; Skin ; Tumor Necrosis Factor-alpha

BACKGROUND: Various allergens and irritants induced the production of reactive oxygen species (ROS) in the well-established mouse dendritic cell (DC) line XS106 and this production of ROS was inhibited by antioxidants. OBJECTIVE: To investigate the production and functions of ROS in mouse bone marrow-derived DCs (BM-DCs) by various haptens and irritants, we examined the production of ROS, the expression of surface molecules, and the production of interleukin-12 (IL-12) in mouse BM-DCs. METHODS: Six to eight-week-old female C57/BL6 mice were used in this study. Mouse BM-DCs were co-cultured with DNFB, DNCB, TNBS, hydroquinone, NiSO4, CoCl2, MnCl2, thimerosal, SDS, and BKC. The production of ROS and the expression of surface molecules (CD40, CD80, CD86, and MHC-II) were measured by flow cytometry in chemical-treated mouse BM-DCs. In addition, the cells were pretreated with antioxidants to determine whether the production of ROS can be inhibited. The production of IL-12 was also measured in DNCB and SDS-treated mouse BM-DCs using ELISA. Results: The production of ROS in mouse BM-DCs was induced by various allergens, including DNFB, DNCB, TNBS, hydroquinone, MnCl2 and irritants like SDS, BKC. The expression of surface molecules was induced by various chemicals and NiSO4 was the most potent inducer of surface molecules in mouse BM-DCs. The production of ROS in DNCB and SDS-treated mouse BM-DCs was partially inhibited by diphenylene iodonium, but not by rotenone, vitamin E, allopurinol, glutathione. The production of IL-12 was not detected in DNCB and SDS-treated mouse BM-DCs. CONCLUSION: The production of ROS was induced in mouse BM-DCs by various allergens and irritants. The expression of surface molecules was also induced by various chemicals. The production of ROS was partially inhibited by DPI. The production of IL-12 was not detected.
Allergens ; Allopurinol ; Animals ; Antioxidants ; Chlorides ; Dendritic Cells ; Dinitrochlorobenzene ; Dinitrofluorobenzene ; Female ; Flow Cytometry ; Glutathione ; Haptens ; Humans ; Hydroquinones ; Interleukin-12 ; Irritants ; Manganese Compounds ; Mice ; Onium Compounds ; Reactive Oxygen Species ; Rotenone ; Thimerosal ; Vitamin E ; Vitamins

This study is to observe the inhibition of etoposide on allergic contact dermatitis (ACD) and explore its possible mechanism of action. Dinitrofluorobenzene was used to induce the allergic contact dermatitis in mouse ear. Three groups of animals were orally administrated with different doses of VP-16 (5, 10, and 20 mg x kg(-1)), separately, for six days. The degree of skin inflammatory reaction was observed by optical microscope. Expression of intercellular adhesion molecule (ICAM-1) was detected by immunohistochemical staining. Radioimmunoassay was applied to measure the serum level of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). VP-16 significantly decreased inflammatory cell infiltration and the degree of infiltration reaction, and decreased the level of TNF-a in serum and the expression of ICAM-l in skin. VP-16 can significantly inhibit allergic contact dermatitis induced by DNFB. This therapeutic effect of VP-16 on murine ACD may be due to inhibiting expression of some cytokines.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Dermatitis, Allergic Contact ; blood ; etiology ; metabolism ; Dinitrofluorobenzene ; Etoposide ; pharmacology ; Female ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-10 ; blood ; Male ; Mice ; Random Allocation ; Skin ; metabolism ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND: Vitamin C is an essential nutrient, taken as a daily supplement by many people. Recently, high-dose vitamin C is considered as a therapeutic regimen in some clinical situations. Until now, few studies have been done with the effects of high-dose vitamin C on the immune response. METHODS: In this experiment, the effects of high-dose vitamin C on cell-mediated immune response in immunologically competent mice were evaluated. After intraperitoneal injection of 2.5, 5, or 10 mg/day of vitamin C for 10 days, delayed type hypersensitivity (DTH) was provoked against DNFB in the pinnae as a model for cell-mediated immune response. Severity of DTH reaction was evaluated as the thickness of pinnae, and the vitamin C levels were measured in the serum, liver, kidney, lung, pinnae, and splenocytes. RESULTS: After challenge, the thickness increased at its peak on the 2(nd) day in all groups. On the first day, the pinnae were thicker in the injected groups than in the control. On the contrary, the increment of the pinnae thickness was attenuated and the number of cells infiltrated in the site of DTH decreased proportionately to the amount of vitamin C administered from the second day on. With vitamin C exogenously given, the serum level peaked at 30 min after injection, and returned abruptly to its basal level without accumulation. However, it accumulated in the liver, kidney, and especially in the pinnae inflamed and splenopcytes, proportionately to the amount administered. CONCLUSION: Based on these results, it is suggested that, in one hand, exogenously administered high-dose vitamin C accumulated in the splenocytes and presumably changed the function of them resulting in the augmented cell-mediated immune response, as was revealed in the first day of DTH reaction. On the other hand, it seems likely that the vitamin C also showed anti-inflammatory effects.
Animals ; Ascorbic Acid* ; Dinitrofluorobenzene ; Hand ; Hypersensitivity ; Injections, Intraperitoneal ; Kidney ; Liver ; Lung ; Mice* ; Vitamins*

BACKGROUND: Evening primrose oil(EPO) is a rich source of cis-linoleic acid and gammalinolenic acid(GLA) and has been used as a therapeutic agent in various skin diseases such as atopic dermatitis. OBJECTIVE: The purpose of this study was to evaluate the suppressive effect of EPO on murine contact sensitivity. METHODS: BALB/c mice were divided into 3 groups, positive control, experimental and negative control groups: the positive control group represents a group of mice which were sensitized and challenged with DNFB, the experimental group represents EPO-pretreated positive control group and the negative control group represents a group of mice which were challenged only. The changes of ear thickness were measured, and H & E staining and immunohistochemical staining for ICAM-1 expression of ear skin were performed to evaluate the histological changes of each group. RESULTS: The Pretreatment of mice with EPO resulted in suppression of contact sensitivity by more than 82%. On H & E staining, only a mild inflammatory reaction was observed in the dermis. Also ICAM-1 expression of keratinocytes, the intensity of the staining was significantly decreased in the experimental group compared with positive group. CONCLUSIONS: Our study indicates that EPO was able to suppress the induction of contact sensitivity.
Animals ; Dermatitis, Atopic ; Dermatitis, Contact* ; Dermis ; Dinitrofluorobenzene ; Ear ; Intercellular Adhesion Molecule-1 ; Keratinocytes ; Mice ; Oenothera biennis* ; Skin ; Skin Diseases