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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 -
BioMed Research International 2021The benefits of emollients for eczematous dermatitis and psoriasis have been thought to be due to the improvements in epidermal function, including epidermal...
The benefits of emollients for eczematous dermatitis and psoriasis have been thought to be due to the improvements in epidermal function, including epidermal permeability barrier, stratum corneum hydration, and stratum corneum pH. We determined here whether emollient can direct inhibit cutaneous inflammation. Ear inflammation was induced by topical application of either 12-O-tetradecanoylphorbol-13-acetate (TPA) or 1-fluoro-2,4-dinitrofluorobenzene (DNFB). Either 1% hydrocortisone cream or the novel emollient was applied to the right ear of the mice 45 min and 2 hours after TPA or DNFB application. The untreated left ear served as untreated controls. Both ear weight and ear thickness were measured 24 hours after TPA and DNFB application. Topical applications of either hydrocortisone cream or emollient significantly decreased both ear thickness and ear weight in comparison to untreated controls. In DNFB model, hydrocortisone significantly lowered expression levels of mRNA for IL-1, IL-1, and TNF, while the emollient markedly decreased expression levels of IL-1 and TNF mRNA. In TPA model, both hydrocortisone and emollient significantly decreased expression levels of IL-1, IL-1, IL-6, and TNF mRNA. In parallel, inflammatory infiltration was also reduced by topical applications of either hydrocortisone or emollient. These results demonstrate that this novel emollient can directly inhibit cutaneous inflammation in murine models of both acute irritant contact dermatitis and acute allergic contact dermatitis. However, whether this emollient could also alleviate eczematous dermatitis in humans remains to be explored.
Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Cytokines; Dermatitis, Allergic Contact; Disease Models, Animal; Emollients; Female; Inflammation; Mice; Mice, Inbred C57BL; Skin
PubMed: 33954180
DOI: 10.1155/2021/5594646 -
Frontiers in Medicine 2021The animal model is an important tool to study the mechanism of disease formation. Different animal models of pruritus have been adopted based on the purpose of...
The animal model is an important tool to study the mechanism of disease formation. Different animal models of pruritus have been adopted based on the purpose of researchers in the study of the itching mechanism. Although the symptoms of various models are quite different, scratching behavior is a key indicator. Therefore, it is necessary to find an animal model that can quickly induce animal scratching and maintain the stability of scratching behavior. In this study, we compared animal models of pruritus induced by four substances and found that the scratching behavior of mice induced by urushiol not only reached the plateau stage quickly but also showed more stability in the plateau phase than that induced by 2,4-dinitrofluorobenzene, oxazolone, and imiquimod. Meanwhile, in the animal model induced by urushiol, the changes of epidermal thickening and inflammatory cell aggregation were also more obvious. In addition, pruritus induced by urushiol is prevalent all over the world, especially in the United States and Europe, involving outdoor groups such as firefighters, forest loggers, and farmers. Therefore, we believe that the urushiol-induced animal model is an ideal choice for the study of the itch formation mechanism and the development of antipruritic drugs.
PubMed: 33708782
DOI: 10.3389/fmed.2021.630237 -
Cells Feb 2021Palmitoylethanolamide (PEA) is an endogenous anti-inflammatory lipid mediator and a widely used nutraceutical. In this study, we designed, realized, and tested a...
Palmitoylethanolamide (PEA) is an endogenous anti-inflammatory lipid mediator and a widely used nutraceutical. In this study, we designed, realized, and tested a drug-carrier conjugate between PEA (the active drug) and glucuronic acid (the carrier). The conjugate, named GLUPEA, was characterized for its capability of increasing PEA levels and exerting anti-inflammatory activity both in vitro and in vivo. GLUPEA treatment, compared to the same concentration of PEA, resulted in higher cellular amounts of PEA and the endocannabinoid 2-arachidonoyl glycerol (2-AG), and increased 2-AG-induced transient receptor potential vanilloid type 1 (TRPV1) channel desensitization to capsaicin. GLUPEA inhibited pro-inflammatory monocyte chemoattractant protein 2 (MCP-2) release from stimulated keratinocytes, and it was almost as efficacious as ultra-micronized PEA at reducing colitis in dinitrobenzene sulfonic acid (DNBS)-injected mice when using the same dose. GLUPEA is a novel pro-drug able to efficiently mimic the anti-inflammatory and endocannabinoid enhancing actions of PEA.
Topics: Amides; Animals; Arachidonic Acids; Calcium; Chemokine CCL8; Colitis; Colon; Dinitrofluorobenzene; Drug Delivery Systems; Endocannabinoids; Ethanolamines; Glucuronic Acid; Glycerides; HEK293 Cells; HaCaT Cells; Humans; Ion Channel Gating; Keratinocytes; Male; Mice, Inbred ICR; Models, Biological; Palmitic Acids; Peroxidase; Poly I-C; TRPV Cation Channels; Mice
PubMed: 33672574
DOI: 10.3390/cells10020450 -
In Vivo (Athens, Greece) 2021Mesenchymal stem cells (MSCs) have been suggested as an alternative therapeutic option in atopic dermatitis. Palatine tonsils are lymphoepithelial tissue located around...
BACKGROUND/AIM
Mesenchymal stem cells (MSCs) have been suggested as an alternative therapeutic option in atopic dermatitis. Palatine tonsils are lymphoepithelial tissue located around the oropharynx and have been proposed as one of the important alternative sources of MSCs. The purpose of this study was to evaluate the protective and therapeutic effects of tonsil-derived MSCs (TMSCs) in a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic dermatitis (AD).
MATERIALS AND METHODS
The effect of TMSCs was evaluated in 20 C57BL/6J mice that were randomly divided into four groups (normal, DNFB-PBS, DNFB-TMSC7, and DNFB-TMSC16 group). TMSCs were subcutaneously injected into DNFB-sensitized mice on day 7 (DNFB-TMSC7 group) and day 16 (DNFB-TMSC16 group). Several parameters of inflammation were assessed.
RESULTS
Subcutaneously injected TMSCs significantly improved the inflammatory symptoms in a DNFB-induced AD model mice, particularly showing therapeutic effects rather than protective effects. TMSC treatment inhibited T-cell-mediated inflammatory responses by decreasing the levels of IL-6, IL-1β, TNF-α (Th1 cell marker), IL-4 (Th2 cell marker), and B-cell-mediated serum IgE. In contrast, TMSCs enhanced the anti-inflammatory cytokine TGF-β.
CONCLUSION
In vitro and in vivo results suggest that TMSC treatment improved inflammatory skin lesions in the DNFB-induced AD mice model via immunomodulatory effects of the TMSCs. TMSCs inhibit T-cell and B-cell mediated responses, and enhance the anti-inflammatory responses.
Topics: Animals; Dermatitis, Atopic; Dinitrofluorobenzene; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Palatine Tonsil
PubMed: 33622877
DOI: 10.21873/invivo.12325 -
Proceedings of the National Academy of... Jan 2021Dysregulation of inflammatory cytokines in keratinocytes promote the pathogenesis of the skin inflammation, such as allergic contact dermatitis (ACD). High-mobility...
Dysregulation of inflammatory cytokines in keratinocytes promote the pathogenesis of the skin inflammation, such as allergic contact dermatitis (ACD). High-mobility group box 1 protein (HMGB1) has been implicated in the promotion of skin inflammation upon its extracellular release as a damage-associated molecular pattern molecule. However, whether and how HMGB1 in keratinocytes contributes to ACD and other skin disorders remain elusive. In this study, we generated conditional knockout mice in which the gene is specifically deleted in keratinocytes, and examined its role in ACD models. Interestingly, the mutant mice showed exacerbated skin inflammation, accompanied by increased ear thickening in 2,4-dinitrofluorobenezene-induced ACDs. The mRNA expression of interleukin-24 (IL-24), a cytokine known to critically contribute to ACD pathogenesis, was elevated in skin lesions of the mutant mice. As with constitutively expressed, IL-4-induced mRNA, expression was also augmented in the -deficient keratinocytes, which would account for the exacerbation of ACD in the mutant mice. Mechanistically, we observed an increased binding of trimethyl histone H3 (lys4) (H3K4me3), a hallmark of transcriptionally active genes, to the promoter region of the gene in the -deficient cells. Thus, the nuclear HMGB1 is a critical "gate keeper" in that the dermal homeostasis is contingent to its function in chromatin remodeling. Our study revealed a facet of nuclear HMGB1, namely its antiinflammatory function in keratinocytes for the skin homeostasis.
Topics: Animals; Chromatin Assembly and Disassembly; Dermatitis, Allergic Contact; Dinitrofluorobenzene; Disease Models, Animal; Ear; Gene Deletion; Gene Expression Regulation; HMGB1 Protein; Histones; Inflammation; Interleukin-4; Interleukins; Keratinocytes; Mice; Mice, Knockout; Promoter Regions, Genetic; Skin; Transplantation Chimera
PubMed: 33443188
DOI: 10.1073/pnas.2022343118 -
Journal of Ginseng Research Jan 2021Atopic dermatitis (AD) is associated with chronic skin inflammatory reactions. -coumaric acid (CA) is an active ingredient of Meyer (Araliaceae).
BACKGROUND
Atopic dermatitis (AD) is associated with chronic skin inflammatory reactions. -coumaric acid (CA) is an active ingredient of Meyer (Araliaceae).
METHODS
Here, we estimated an anti-AD effect of CA on activated mast cells, activated splenocytes, and a mouse model of AD. Cytokines levels were measured by ELISA and protein activation was analyzed by Western blotting. 2,4-dinitrofluorobenzene (DNFB) was used to induce AD-like skin lesions.
RESULTS
The treatment with CA suppressed the productions and mRNA expressions of thymic stromal lymphopoietin (TSLP), TNF-ɑ, IL-6, and IL-1β in HMC-1 cells. CA downregulated the expressions of RIP2 and caspase-1, phosphorylated-(p)p38/pJNK/pERK, and pIKKβ/pIkBɑ/NF-κB in HMC-1 cells. CA also decreased the productions of TSLP, TNF-ɑ, IL-6, IL-4, and IFN-γ in the supernatant of stimulated splenic cells. Comparing to DNFB-sensitized control group, CA-treated group alleviated pathological changes of AD-like lesions. CA decreased the proteins and mRNA expressions levels of TSLP, IL-6, and IL-4 in the skin lesions. Caspase-1 activation was also downregulated by CA treatment in the AD-like lesions. The serum levels of histamine, IgE, TSLP, TNF-ɑ, IL-6, and IL-4 were suppressed following treatment with CA.
CONCLUSION
This study suggests that CA has the potential to improve AD by suppressing TSLP as well as inflammatory cytokines via blocking of caspase-1/NF-κB signal cascade.
PubMed: 33437169
DOI: 10.1016/j.jgr.2020.06.004 -
The Journal of Allergy and Clinical... Jun 2021Atopic dermatitis (AD) is characterized by a skin barrier defect aggravated by mechanical injury inflicted by scratching, a T2 cell-dominated immune response, and...
BACKGROUND
Atopic dermatitis (AD) is characterized by a skin barrier defect aggravated by mechanical injury inflicted by scratching, a T2 cell-dominated immune response, and susceptibility to viral skin infections that are normally restrained by a T1 cell response. The signals leading to a T2 cell-dominated immune response in AD are not completely understood.
OBJECTIVE
Our aim was to determine the role of IL-13 in initiation of the T cell response to cutaneously encountered antigens.
METHODS
Wild-type, Il13, Il1rl1, and Il4ra mice, as well as mice with selective deficiency of IL-13 in mast cells (MCs) were studied; in addition, dendritic cells (DCs) purified from the draining lymph nodes of tape-stripped and ovalbumin (OVA)-sensitized skin were examined for their ability to polarize naive OVA-TCR transgenic CD4 T cells. Cytokine expression was examined by reverse-transcriptase quantitative PCR, intracellular flow cytometry, and ELISA. Contact hypersensitivity to dinitrofluorobenzene was examined.
RESULTS
Tape stripping caused IL-33-driven upregulation of Il13 expression by skin MCs. MC-derived IL-13 acted on DCs from draining lymph nodes of OVA-sensitized skin to selectively suppress their ability to polarize naive OVA-TCR transgenic CD4 T cells into IFN-γ-secreting cells. MC-derived IL-13 inhibited the T1 cell response in contact hypersensitivity to dinitrofluorobenzene. IL-13 suppressed IL-12 production by mouse skin-derived DCs in vitro and in vivo. Scratching upregulated IL13 expression in human skin, and IL-13 suppressed the capacity of LPS-stimulated human skin DCs to express IL-12 and promote IFN-γ secretion by CD4 T cells.
CONCLUSION
Release of IL-13 by cutaneous MCs in response to mechanical skin injury inhibits the T1 cell response to cutaneous antigen exposure in AD.
Topics: Animals; Antigens; Cytokines; Dendritic Cells; Dermatitis, Atopic; Disease Models, Animal; Humans; Interleukin-12; Interleukin-13; Mast Cells; Mice; Mice, Knockout; T-Lymphocyte Subsets; Th1 Cells
PubMed: 33316284
DOI: 10.1016/j.jaci.2020.11.036 -
BMB Reports Apr 2021Lysophosphatidylcholine (LPC) is a bioactive lysolipid known to contribute to the development of lung allergic diseases. However, it remains unknown whether LPC...
Lysophosphatidylcholine (LPC) is a bioactive lysolipid known to contribute to the development of lung allergic diseases. However, it remains unknown whether LPC possesses proinflammatory properties in the skin as well. Here, we investigated this issue by injection of LPC into the murine contact hypersensitivity (CHS) model induced by 2,4-dinitrofluorobenzene (DNFB). LPC increased the expression of IL17, recruited more neutrophils, and eventually aggravated the CHS in the skins. Moreover, the effects of LPC diminished after neutralizing IL17 or depleting neutrophils. Mechanistically, LPC upregulated not only IL17 but also CXCL1 and CXCL2 in a G2A-dependent manner. Taken together, our study demonstrated that the upregulation of LPC could contribute to allergic skin inflammation by increasing IL17 expression and neutrophil recruitment via G2A receptor. [BMB Reports 2021; 54(4): 203-208].
Topics: Animals; Cell Cycle Proteins; Dermatitis, Contact; Dinitrofluorobenzene; Disease Models, Animal; Injections, Subcutaneous; Interleukin-17; Lysophosphatidylcholines; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration; Receptors, G-Protein-Coupled
PubMed: 33172544
DOI: 10.5483/BMBRep.2021.54.4.193 -
Allergy Jun 2021Fatty acid-binding protein 3 (FABP3) is a cytosolic carrier protein of polyunsaturated fatty acids (PUFAs) and regulates cellular metabolism. However, the physiological...
BACKGROUND
Fatty acid-binding protein 3 (FABP3) is a cytosolic carrier protein of polyunsaturated fatty acids (PUFAs) and regulates cellular metabolism. However, the physiological functions of FABP3 in immune cells and how FABP3 regulates inflammatory responses remain unclear.
METHODS
Contact hypersensitivity (CHS) induced by 2,4-dinitrofluorobenzene (DNFB) and fluorescein isothiocyanate was applied to the skin wild-type and Fabp3 mice. Skin inflammation was assessed using FACS, histological, and qPCR analyses. The development of γ/δ T cells was evaluated by a co-culture system with OP9/Dll1 cells in the presence or absence of transgene of FABP3.
RESULTS
Fabp3-deficient mice exhibit a more severe phenotype of contact hypersensitivity (CHS) accompanied by infiltration of IL-17-producing Vγ4 γ/δ T cells that critically control skin inflammation. In Fabp3 mice, we found a larger proportion of Vγ4 γ/δ T cells in the skin, even though the percentage of total γ/δ T cells did not change at steady state. Similarly, juvenile Fabp3 mice also contained a higher amount of Vγ4 γ/δ T cells not only in the skin but in the thymus when compared with wild-type mice. Furthermore, thymic double-negative (DN) cells expressed FABP3, and FABP3 negatively regulates the development of Vγ4 γ/δ T cells in the thymus.
CONCLUSIONS
These findings suggest that FABP3 functions as a negative regulator of skin inflammation through limiting pathogenic Vγ4 γ/δ T-cell generation in the thymus.
Topics: Animals; Dermatitis, Contact; Disease Models, Animal; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Mice; Mice, Inbred C57BL; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocytes
PubMed: 33090507
DOI: 10.1111/all.14630