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Clinical and Experimental Immunology Jan 2019Soyasaponins (SSs) are abundant in soybeans and display inhibitory activity against contact hypersensitivity (CHS), which is often used as a mouse model for allergic...
Soyasaponins (SSs) are abundant in soybeans and display inhibitory activity against contact hypersensitivity (CHS), which is often used as a mouse model for allergic contact dermatitis (ACD); however, their therapeutic mechanisms remain unknown. Here, we attempted to clarify the role of gut microbiota in the inhibition of CHS by dietary soyasaponins. For antibiotic treatment, mice were administered a mixture of ciprofloxacin and metronidazole or vancomycin. These antibiotics and SSs were given to mice via drinking water 3-weeks prior to CHS induction with 2,4-dinitrofluorobenzene, and the mice were analysed for ear swelling, tissue oedema, infiltration of Gr-1-positive immune cells, the composition of faecal microbiota and regulatory T (T ) cells. The soyasaponin diets attenuated ear swelling and tissue oedema, and reduced the number of Gr-1-positive cells infiltrating ear tissues. CHS caused changes in the structure of the gut microbiota, but dietary SSs blocked the changes in the microbiota composition. Ciprofloxacin and metronidazole treatments significantly enhanced the severity of CHS symptoms, whereas vancomycin treatment blocked the suppressive effect of dietary SSs on CHS. These antibiotic treatments differed in their effects on the gut microbiota composition. T cells in auricular lymph node and spleen increased under SS-enriched diets, but this increase was blocked by vancomycin treatment. These results suggest that dietary SSs exert their inhibitory activity on CHS via the gut microbiota in mice, suggesting that dietary supplementation with SSs may have beneficial effects on ACD patients, but that the gut microbiota is a critical determinant of the therapeutic value of dietary SSs.
Topics: Animals; Anti-Bacterial Agents; Cells, Cultured; Dermatitis, Allergic Contact; Dermatitis, Contact; Diet; Dinitrofluorobenzene; Disease Models, Animal; Edema; Female; Gastrointestinal Microbiome; Humans; Mice; Mice, Inbred BALB C; Saponins; Glycine max; T-Lymphocytes, Regulatory
PubMed: 30178467
DOI: 10.1111/cei.13212 -
International Journal of Food Sciences... Aug 2019Soymilk is rich in phytochemicals such as soy isoflavones (SIs) and soyasaponins (SSs). Dietary SIs and SSs display inhibitory effects on contact hypersensitivity (CHS),...
Soymilk is rich in phytochemicals such as soy isoflavones (SIs) and soyasaponins (SSs). Dietary SIs and SSs display inhibitory effects on contact hypersensitivity (CHS), which was reported in a mouse model for allergic contact dermatitis (ACD); however, the beneficial effects of soymilk consumption on CHS remain unknown. Here, we studied the effects of drinking soymilk on CHS and gut microbiota. Soymilk consumption attenuated ear oedema and swelling, decreased the infiltration of Gr-1-positive cells into ear tissues, and reduced the production of chemokine (C-X-C motif) ligand 2 and triggering receptor expressed on myeloid cells-1 in ear tissues. The analysis of bacterial 16S ribosomal RNA gene sequences indicated that CHS caused changes in the gut microbiota structure and that consuming soymilk reduced these changes. These results suggest that soymilk consumption may be of therapeutic value for patients with ACD and may help control the balance of intestinal microbiota.
Topics: Animals; Bacteria; Chemokine CXCL2; Cytokines; Dermatitis, Contact; Diet; Dinitrofluorobenzene; Disease Models, Animal; Ear; Edema; Female; Gastrointestinal Microbiome; Humans; Isoflavones; Mice; Mice, Inbred BALB C; Phytochemicals; RNA, Ribosomal, 16S; Saponins; Soy Milk; Triggering Receptor Expressed on Myeloid Cells-1
PubMed: 30501551
DOI: 10.1080/09637486.2018.1547689 -
Contact Dermatitis Oct 2023Poly(I:C) is recognised by endosomal Toll-like receptor 3 (TLR3) and activates cytotoxic CD8(+) lymphocytes and natural killer (NK) cells. It has been shown that the...
INTRODUCTION
Poly(I:C) is recognised by endosomal Toll-like receptor 3 (TLR3) and activates cytotoxic CD8(+) lymphocytes and natural killer (NK) cells. It has been shown that the viral TLR3 agonist induces robust and long-lasting T-cell-mediated responses. In addition, TLR3 modulates the contact hypersensitivity reaction.
OBJECTIVE
This study aimed to determine whether poly(I:C) injection can induce NK-mediated hapten reactivity in mice.
METHODS
Mice were treated with poly(I:C), and their response to dinitrofluorobenzene hapten was measured by assessing ear swelling and serum interferon gamma (IFN-γ) production. Adoptive cell transfer and cell sorting were used to investigate the mechanism of the reaction, and the phenotype of poly(I:C)-activated liver NK cells was determined by flow cytometry analysis.
RESULTS
The results showed that poly(I:C) administration increased ear swelling, serum IFN-γ levels and the response to hapten in both immunocompetent and T- and B-cell-deficient mice. Only liver poly(I:C)-activated DX5(+) NK cells were able to transfer reactivity to hapten into a naive recipient. Induction of liver NK cells after poly(I:C) administration was TLR3/TRIF- and IFN-γ-dependent, interleukin 12-independent, and not modulated by MyD88.
CONCLUSION
This study provides new insights into how poly(I:C) stimulates NK-mediated reactivity to hapten and suggests that liver NK cells may modulate the immune response to non-pathogenic factors during viral infection.
Topics: Mice; Animals; Toll-Like Receptor 3; Ligands; Dermatitis, Allergic Contact; Killer Cells, Natural; Poly I-C; Interferon-gamma; Mice, Inbred C57BL
PubMed: 37463838
DOI: 10.1111/cod.14380 -
Immunity, Inflammation and Disease Apr 2022Contact hypersensitivity (CHS), a type of delayed-type hypersensitivity, is induced by hapten exposure to the skin and mucosa. We previously reported that, in a murine... (Comparative Study)
Comparative Study
INTRODUCTION
Contact hypersensitivity (CHS), a type of delayed-type hypersensitivity, is induced by hapten exposure to the skin and mucosa. We previously reported that, in a murine model of CHS, the vaginal mucosa (VM) sensitization showed lower T-cell responses as compared with the abdominal skin sensitization. To investigate mechanisms of impaired CHS by the VM sensitization, we compared migration of hapten-captured dendritic cells (DCs) in the draining lymph nodes (dLNs) and recruitment of DCs at the sensitized local sites.
METHODS
Fluorescein isothiocyanate (FITC) or 2,4-dinitrofluorobenzene (DNFB) was used as hapten, and migration of FITC DCs in the dLNs and local recruitment of MHC class II and CD11c cells were compared between abdominal skin and VM sensitization by flow cytometric analyses and immunohistochemistry. Expression of tumor growth factor (TGF)-β at mRNA and protein levels, and local recruitment of CD206 cells were examined after VM sensitization.
RESULTS
VM sensitization showed less numbers of FITC MHC class II CD11c migratory DCs in the dLNs at 6 and 24 h, as compared with skin sensitization. Both skin and VM sensitization induced the recruitment of dermal/submucosal DCs at 6 h, but the number of submucosal DCs in the VM was significantly decreased at 24 h. VM showed persistently higher mRNA levels of TGF-β2/β3 expression than those of the skin before and after sensitization. In the VM sensitization, increment of CD206 MHC class II cells was observed especially at the deep lamina propria at 24 h. Most of CD206 cells were also positive for the binding to Fc chimeric TGF-β receptor that interacts with all TGF-β isoforms, suggesting TGF-β expression.
CONCLUSION
DC migration to dLNs and localization of DCs at the sensitized sites are limited in the VM sensitization. Our results suggest that the existence of TGF-β-expressing CD206 cells may contribute less sensitization ability and CHS responses in the VM.
Topics: Animals; Dendritic Cells; Female; Haptens; Mice; Mice, Inbred C57BL; Mucous Membrane; Transforming Growth Factor beta
PubMed: 35349751
DOI: 10.1002/iid3.605 -
European Journal of Pharmacology Dec 2023Programmed cell death receptor/ligand 1 (PD-1/PD-L1) blockade therapy for various cancers induces itch. However, few studies have evaluated the mechanism underlying...
Programmed cell death receptor/ligand 1 (PD-1/PD-L1) blockade therapy for various cancers induces itch. However, few studies have evaluated the mechanism underlying PD-1/PD-L1 inhibitor-induced itch. This study aimed to establish and evaluate a mouse model of acute itch induced by PD-1/PD-L1 inhibitors and to explore the role of the PD-1/PD-L1 pathway in chronic itch. The intradermal injection of the PD-1/PD-L1 small molecule inhibitors, or anti-PD-1/PD-L1 antibodies in the nape of the neck in the mice elicited intense spontaneous scratches. The model was evaluated using pharmacological methods. The number of scratches was reduced by naloxone but not by antihistamines or the transient receptor potential (TRP) channel inhibitor. Moreover, the PD-1 receptor was detected in the spinal cord of the mouse models of chronic itch that exhibited acetone, diethyl ether, and water (AEW)-induced dry skin, imiquimod-induced psoriasis, and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced allergic contact dermatitis. Intrathecal PD-L1 (1 μg, 4 times a week for 1 week) suppressed the activation of the microglia in the spinal dorsal horn to relieve the chronic itch that was elicited by imiquimod-induced psoriasis and DNFB-induced allergic contact dermatitis. Although the activation of the microglia in the spinal dorsal horn was not detected in the AEW-treated mice, intrathecal PD-L1 still reduced the number of scratches that were elicited by AEW. Our findings suggest that histamine receptor inhibitors or TRP channel inhibitors have limited effects on PD-1/PD-L1 inhibitor-induced itch and that spinal PD-1 is important for the spinal activation of the microglia, which may underlie chronic itch.
Topics: Animals; Mice; Programmed Cell Death 1 Receptor; Dinitrofluorobenzene; B7-H1 Antigen; Imiquimod; Immune Checkpoint Inhibitors; Pruritus; Spinal Cord Dorsal Horn; Dermatitis, Allergic Contact; Disease Models, Animal; Psoriasis; Mice, Inbred C57BL
PubMed: 37866747
DOI: 10.1016/j.ejphar.2023.176128 -
Contact Dermatitis Mar 2019Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown.
BACKGROUND
Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown.
OBJECTIVES
To investigate whether filaggrin-deficient flaky tail (ft/ft) mice show increased immune reactivity to nickel and elucidate the mechanisms mediating this.
METHODS
The immune responses to nickel, 2,4-dinitrofluorobenzene (DNFB), cinnamal and p-phenylenediamine were assessed in ft/ft and wild-type (WT) mice. The amounts of nickel in the skin of ft/ft and WT mice were determined 20 hours after nickel exposure. The effect of blocking either the interleukin (IL)-17A pathway or the IL-1 pathway on the response to nickel in ft/ft mice was evaluated.
RESULTS
Increased responsiveness to nickel, DNFB and cinnamal was observed in ft/ft mice as compared with controls. A reduced amount of nickel was found in the skin of ft/ft mice as compared with WT mice, suggesting increased nickel absorption by the skin of ft/ft mice. Blocking either the IL-17A pathway or the IL-1 pathway reduced nickel responsiveness in ft/ft mice.
CONCLUSIONS
These findings suggest that the increased nickel responsiveness associated with epidermal filaggrin deficiency is mediated by a combination of increased nickel penetration and the steady-state inflammation found in the skin of filaggrin-deficient mice.
Topics: Allergens; Animals; Cytokines; Dermatitis, Atopic; Filaggrin Proteins; Intermediate Filament Proteins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nickel; Skin
PubMed: 30426511
DOI: 10.1111/cod.13153 -
International Immunopharmacology Jul 2019Imiquimod (Imiq) is a synthetic imizoquinoline compound which can act on Toll-like receptor (TLR)7 and transduce signals involved in cell activation. We investigated the...
Imiquimod (Imiq) is a synthetic imizoquinoline compound which can act on Toll-like receptor (TLR)7 and transduce signals involved in cell activation. We investigated the role of Imiq on contact hypersensitivity (CHS) and explored the potential mechanisms of mast cells involved in the process. Topical application of Imiq cream augmented DNFB mediated CHS in C57BL/6 mice. Imiq application induced skin inflammation and increased the number of dendritic cells (DCs) in the draining lymph nodes (DLNs). The splenic cell proliferation to DNBS in DNFB and Imiq treated mice was greater than that in mice of DNFB treatment alone. Peritoneal cell-derived mast cells (PCMCs) expressed TLR7 mRNA. The results from toluidine blue staining for mast cells and histamine detection indicated that Imiq alone did not induce mast cell degranulation while Imiq plus DNFB significantly induced mast cell degranulation. Cromolyn, pyrilamine and cimetidine attenuated CHS reaction induced by Imiq. Our findings suggest that Imiq could augment the intensity of CHS reaction. The mechanisms underlying the effect may relate to histamine release by mast cells and induction of DC homing to DLNs. Blocking histamine action in early time of allergen contact is beneficial to the alleviation of CHS.
Topics: Adjuvants, Immunologic; Administration, Topical; Animals; Cell Proliferation; Dendritic Cells; Dermatitis, Contact; Dinitrofluorobenzene; Female; Histamine; Imiquimod; Lymph Nodes; Mast Cells; Mice, Inbred C57BL; Spleen
PubMed: 31005038
DOI: 10.1016/j.intimp.2019.04.025 -
Biochemical and Biophysical Research... Nov 2021Although allergic contact dermatitis (ACD) is the most common T cell-mediated inflammatory responses against an allergen in the skin, the pathogenesis of ACD remains...
Although allergic contact dermatitis (ACD) is the most common T cell-mediated inflammatory responses against an allergen in the skin, the pathogenesis of ACD remains incompletely understood. In the sensitization phase in ACD, hapten-bearing dermal dendritic cells (DCs) play a pivotal role in the transport of an antigen to the lymph nodes (LNs), where they present the antigen to naïve T cells. Here we report that Allergin-1, an inhibitory immunoreceptor containing immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic region, is highly expressed on dermal DCs. Mice deficient in Allergin-1 exhibited exacerbated fluorescein isothiocyanate (FITC)-induced type 2 contact hypersensitivity (CHS) such as ear swelling and skin eosinophilia. Allergin-1-deficient mice also showed larger numbers of CD4 T cells and FITC-bearing DCs and greater expressions of type 2 cytokines, including IL-5, IL-10 and IL-13, in the draining LNs than did wild type mice. In sharp contrast, Allergin-1-deficient mice showed comparable level of type 1 CHS induced by 2,4-dinitrofluorobenzene (DNFB). These results suggest that Allergin-1 on dermal DC inhibits type 2, but not type 1, immune responses in the sensitization phase of CHS.
Topics: Animals; CD4-Positive T-Lymphocytes; Dendritic Cells; Dermatitis, Contact; Dinitrofluorobenzene; Female; Fluorescein-5-isothiocyanate; Hypersensitivity, Immediate; Interleukin-10; Interleukin-13; Interleukin-5; Mice; Mice, Inbred BALB C; Receptors, Immunologic; Skin
PubMed: 34601199
DOI: 10.1016/j.bbrc.2021.09.048 -
Frontiers in Pharmacology 2021Depression and contact dermatitis (CD) are considered relatively common health problems that are linked with psychological stress. The antioxidant, anti-inflammatory,...
Depression and contact dermatitis (CD) are considered relatively common health problems that are linked with psychological stress. The antioxidant, anti-inflammatory, and antidepressant activities of pumpkin were previously reported. This study aimed to evaluate the efficacy of the combined topical and oral application of pumpkin fruit ( L.) extract (PE) in relieving CD associated with chronic stress-induced depression and compare it to the topical pumpkin extract alone and to the standard treatment. Forty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression and then exposed to (1-fluoro-2, 4-dinitrofluorobenzene, DNFB) for 2 weeks for induction of CD. Those rats were assigned into 4 groups ( = 10 each); untreated, betamethasone-treated, PE-treated and pumpkin extract cream, and oral-treated groups. Treatments were continued for 2 weeks. All groups were compared to the negative control group ( = 10). Depression was behaviorally and biochemically confirmed. Serum and mRNA levels of pro-inflammatory cytokines, such as TNF-α, IL-6, COX-2, and iNOS, were assessed. Oxidant/antioxidant profile was assessed in the serum and skin. Histopathological and immunohistochemical assessments of affected skin samples were performed. Pumpkin extract, used in this study, included a large amount of oleic acid (about 56%). The combined topical and oral administration of PE significantly reduced inflammatory and oxidative changes induced by CD and depression compared to the CD standard treatment and to the topical PE alone. PE significantly alleviated CD signs and the histopathological score ( < 0.001) mostly through the downregulation of pro-inflammatory cytokines and the upregulation of antioxidants. Pumpkin extract, applied topically and orally, could be an alternative and/or complementary approach for treating contact dermatitis associated with depression. Further studies on volunteer patients of contact dermatitis are recommended.
PubMed: 34040528
DOI: 10.3389/fphar.2021.663417 -
Journal of Ethnopharmacology May 2022Lepidium virginicum L. (Brassicaceae) is a plant widely used in traditional Mexican medicine as an expectorant, diuretic, and as a remedy to treat diarrhea and...
ETHNOPHARMACOLOGICAL RELEVANCE
Lepidium virginicum L. (Brassicaceae) is a plant widely used in traditional Mexican medicine as an expectorant, diuretic, and as a remedy to treat diarrhea and dysentery, infection-derived gastroenteritis. However, there is no scientific study that validates its clinical use as an anti-inflammatory in the intestine.
AIM OF THE STUDY
This study aimed to investigate the anti-inflammatory properties of the ethanolic extract of Lepidium virginicum L. (ELv) in an animal model of inflammatory bowel disease (IBD)-like colitis.
MATERIALS AND METHODS
The 2,4-dinitrobenzene sulfonic acid (DNBS) animal model of IBD was used. Colitis was induced by intrarectal instillation of 200 mg/kg of DNBS dissolved vehicle, 50% ethanol. Control rats only received the vehicle. Six hours posterior to DNBS administration, ELv (3, 30, or 100 mg/kg) was administered daily by gavage or intraperitoneal injection. The onset and course of the inflammatory response were monitored by assessing weight loss, stool consistency, and fecal blood. Colonic damage was evaluated by colon weight/length ratio, histopathology, colonic myeloperoxidase (MPO) activity, and gene expression of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), chemokine C-X-C motif ligand 1 (CXCL-1), and interleukin-6 (IL-6).
RESULTS
Rats treated with DNBS displayed significant weight loss, diarrhea, fecal blood, colon shortening, a significant increase in immune cell infiltration and MPO activity, as well as increased proinflammatory cytokine expression. Intraperitoneal administration of ELv significantly reduced colon inflammation, whereas oral treatment proved to be ineffective. In fact, intraperitoneal ELv significantly attenuated the clinical manifestations of colitis, immune cell infiltration, MPO activity, and pro-inflammatory (CXCL-1, TNF-α, and IL-1β) gene expression in a dose-dependent manner.
CONCLUSION
Traditional medicine has employed ELv as a remedy for common infection-derived gastrointestinal symptoms; however, we hereby present the first published study validating its anti-inflammatory properties in the mitigation of DNBS-induced colitis.
Topics: Animals; Anti-Inflammatory Agents; Colitis; Dinitrofluorobenzene; Dose-Response Relationship, Drug; Ethanol; Female; Gene Expression Regulation; Inflammatory Bowel Diseases; Lepidium; Medicine, Traditional; Plant Extracts; Rats; Rats, Wistar
PubMed: 35104576
DOI: 10.1016/j.jep.2022.115056