Secoisolariciresinol diglucoside inhibits imiquimod-induced psoriatic inflammation in mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Shulin Liu
PROVIDER: PXD068851 | iProX | Fri Sep 26 00:00:00 GMT+01:00 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations to essentially develop safe and effective treatments. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model. It is primarily used to assess safety and efficacy of drug candidates for treatment of psoriasis but can also be used to evaluate the performance of drug delivery systems. In this model, topically applied IMQ provokes local skin inflammation, which is characterized by elevated levels of cytokines and chemokines, cellular infiltration, and increased epidermal thickness. In this study, we investigated the abundance of a subset of matrix metalloproteinases (MMPs) in skin from mice with IMQ-induced skin inflammation and skin from naïve mice using targeted proteomics. Our findings revealed a significant increase in the abundance of MMP-2, MMP-7, MMP-8, and MMP-13 after treatment with IMQ compared to the control skin, while MMP-3, MMP-9, and MMP-10 were exclusively detected in the IMQ-treated skin. The increased abundance and broader representation of MMPs in the IMQ-treated skin provide valuable insight into the pathophysiology of skin inflammation in the IMQ model. Specifically, the changes in the MMP profiles observed in the IMQ-treated skin resemble the MMP patterns found in skin lesions of individuals with psoriasis. Ultimately, the differences in MMP abundance under IMQ-induced inflammation as compared to non-inflamed control skin can be exploited as a model to investigate drug efficacy or performance of drug delivery systems.
2025-10-31 | PXD046049 | panorama
Project description:Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B–induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRb-/- or Rag1-/-). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FceRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD. A total of six samples were analyzed. Back skin samples from healthy or AD-induced C57BL/6, PLC-beta 3 KO (C57BL/6 background), and NC/Nga mice were collected for total RNA extraction. Pooled RNA from 2-4 mice per condition were used for analysis.
2013-12-10 | E-GEOD-53132 | biostudies-arrayexpress
Project description:Cutaneous exposure to food antigen through impaired skin barrier has been shown to induce epicutaneous sensitization, and thereby cause IgE-mediated food allergy. We examined whether skin barrier impairment deteriorated food allergy symptoms in epicutaneously sensitized mice. To clarify the association between skin inflammation and food allergy symptoms, we analyzed gene expression at skin lesions using a GeneChip.
2017-06-30 | GSE95278 | GEO
Project description:Mice with epidermal keratinocyte specific knockout of OTULIN develop inflammatory skin disease. To study the inflammatory response we used Lexogen 3´mRNA sequencing to compare the gene expression profiles in the skin of OTULIN epidermis specific knockout and control mice.
2021-08-23 | GSE180024 | GEO
Project description:Genipin is a natural blue colorant in food industry. Inflammation is correlated with human disorders, and nuclear factor-κB (NF-κB) is the critical molecule involved in inflammation. In this study, the anti-inflammatory effect of genipin on the lipopolysaccharide (LPS)-induced acute systemic inflammation in mice was evaluated by NF-κB bioluminescence-guided transcriptomic analysis. Transgenic mice carrying the NF-κB-driven luciferase genes were administered intraperitoneally with LPS and various amounts of genipin. Bioluminescent imaging showed that genipin significantly suppressed LPS-induced NF-κB-dependent luminescence in vivo. The suppression of LPS-induced acute inflammation by genipin was further evidenced by the reductions of cytokine levels in sera and organs. Microarray analysis of these organs showed that the transcripts of 79 genes were differentially expressed in both LPS and LPS/genipin groups, and one third of these genes belonged to chemokine ligand, chemokine receptor, and interferon (IFN)-induced protein genes. Moreover, network analysis showed that NF-κB played a critical role in the regulation of genipin-affected gene expression. In conclusion, we newly identified that genipin exhibited anti-inflammatory effects in a model of LPSinduced acute systemic inflammation via downregulation of chemokine ligand, chemokine receptor, and IFN-induced protein productions. A total of 25 transgenic mice (female, 6 to 8 weeks old) were randomly divided into five groups of five mice: (1) mock, no treatment; (2) LPS (4 mg/kg), (3) LPS plus genipin (1 mg/kg), (4) LPS plus genipin (10 mg/kg), and (5) LPS plus genipin (100 mg/kg). Mice were challenged intraperitoneally with LPS and then with genipin 10 min later. Four hours later, mice were imaged for the luciferase activity, and subsequently sacrificed for ex vivo imaging, RNA extraction, and immunohistochemical staining.
2012-02-25 | E-GEOD-35934 | biostudies-arrayexpress
Project description:Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B–induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRb-/- or Rag1-/-). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FceRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD.
2013-12-10 | GSE53132 | GEO
Project description:We have previously shown that nano-sized graphene oxide (NGO) displays anti-inflammatory activities against natural killer T (NKT) cell-mediated sepsis. To address whether NGO could be applied to treat acute skin inflammation. We developed a conventional skin Cetaphil® cream containing NGO (NGO cream) for topical application to skin lesions and investigated its therapeutic efficacy by employing the tape-stripping-induced acute skin inflammation model. Topical application of NGO cream to the wounded area significantly reduced skin lesions compared with the control cream. Moreover, NGO cream treatment prevented the tape-stripping-elicited infiltration of and IL1β production by skin neutrophils and dendritic cells (DCs). Furthermore, such anti-inflammatory effects of NGO cream were attributed to decreased infiltration of IL12-producing DCs and IFNγ-producing cells (e.g., CD4+ T, CD8+ T, γδ T, NK, and NKT cells) into the skin. In addition, topical NGO cream administration enhanced the expression of suppressive molecules such as FR4 on skin regulatory T cells. Through RNA sequencing analysis, we found that the preventive effect of NGO cream on acute skin inflammation may be correlated with the activation of keratinocytes located in the epidermis. Our results support NGO cream as a therapeutic option to control acute skin inflammation.
2024-08-20 | GSE272008 | GEO
Project description:Pulmonary fibrosis is often triggered by an epithelial injury resulting in the formation of fibrotic lesions in the lung, which progress to impair gas exchange and ultimately cause death. Recent clinical trials using drugs that target either inflammation or a specific molecule have failed, suggesting that multiple pathways and cellular processes need to be attenuated for effective reversal of established and progressive fibrosis. Although activation of MAPK and PI3K pathways have been detected in human fibrotic lung samples, the therapeutic benefits of in vivo modulation of the MAPK and PI3K pathways in combination are unknown. Overexpression of TGF? in the lung epithelium of transgenic mice results in the formation of fibrotic lesions similar to those found in human pulmonary fibrosis, and previous work from our group shows that inhibitors of either the MAPK or PI3K pathway can alter the progression of fibrosis. In this study, we sought to determine whether simultaneous inhibition of the MAPK and PI3K signaling pathways is a more effective therapeutic strategy for established and progressive pulmonary fibrosis. Our results showed that inhibiting both pathways had additive effects compared to inhibiting either pathway alone in reducing fibrotic burden, including reducing lung weight, pleural thickness, and total collagen in the lungs of TGF? mice. This study demonstrates that inhibiting MEK and PI3K in combination abolishes proliferative gene changes associated with fibrosis and myfibroblast accumulation and thus may serve as a therapeutic option in the treatment of human fibrotic lung disease where these pathways play a role. mRNA profiles of CCSP/TGFalpha mice treated with vehicle, ARRY, PX-866, ARRY/PX-866
2013-12-03 | E-GEOD-52854 | biostudies-arrayexpress
Project description:We analyzed epidermal samples from keratinocyte-specific knockout Mettl3 (K14CreERT2;Mettl3fl/fl) mice and their controls (Mettl3fl/fl) in imiquimod-induced psoriasis-like skin lesions. Briefly, we established an imiquimod-induced psoriasis model in K14CreERT2;Mettl3fl/fl mice and their controls after tamoxifen injection, and epidermal samples were separated and collected from the skin lesions of the mice after 3 or 6 days of modeling (n=3 per group). The aim of this study was to investigate the mechanism by which Mettl3-mediated epidermal m6A methylation affects skin inflammation.
2024-08-20 | GSE268745 | GEO
Project description:TRPV3 is highly expressed in human skin and is involved in the development of inflammatory dermatoses. However, it remains unclear whether TRPV3 influences inflammation in human sebaceous glands and its role in the pathogenesis of acne. Here, we showed that TRPV3 expression was increased in the sebaceous glands of facial acne lesions and acne-like mice. TRPV3 increased the secretion of pro-inflammatory cytokines and chemokines in human SZ95 sebocytes, as well as the chemotaxis of neutrophils, which were the major immune cells found in acne lesions. We demonstrated that P.acnes promoted TRPV3 expression through regulating lipid profile especially upregulated arachidonic acid levels in human sebocytes. TRPV3 further upregulated TLR2 expression by promoting transcriptional factor p-FOSL1 expression and its binding to the TLR2 promoter, leading to downstream NF-κB signaling activation. Importantly, either genetic silencing or pharmacological inhibition of TRPV3 alleviated acne-like inflammation in mice, showing reduced acne-characteristic cytokines and chemokines production and neutrophil infiltration by inhibiting the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebocytes inflammation, which was involved in the development of acne, indicating that TRPV3 is a potential therapeutic target for acne and other disorders of the pilosebaceous unit.
2023-10-13 | GSE245001 | GEO