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Amelioration of imiquimod-induced psoriasis-like dermatitis in mice by DSW therapy inspired hydrogel.

ABSTRACT: Psoriasis is a long-lasting and recurrent autoimmune disease which is incurable so far. Dead Sea water (DSW) therapy is an effective approach to help control the symptoms of psoriasis due to the abundant mineral ions in DSW, which inspired the material formulation in this study. Rubidium-Sodium alginate/Polyacrylamide hydrogels (Rb-SA/PAAm gels) composed of sodium alginate and polyacrylamide interpenetrating network structure with different concentrations of rubidium and certain magnesium and zinc content were prepared for the treatment of psoriasis. The obtained results suggest the good mechanical properties of the Rb-SA/PAAm gels including toughness and swelling performance. In terms of in vitro tests, the Rb-SA/PAAm gels not only show nontoxicity to human keratinocyte cell line (Hacats) but also inhibits the activity against inflammatory NF-κβ signaling pathway. Meanwhile, they can release Rb⁺ which enable the Rb-SA/PAAm gels have better antibacterial ability to Streptococcus and Escherichia coli. The results obtained from in vivo tests indicate that these hydrogels could alleviate the symptoms of psoriasis caused by Imiquimod (IMQ) in mice by reducing the inflammatory factor in STAT3 pathway and therefore reduce the immune stimulation of the spleen. In conclusion, the 100Rb-SA/PAAm gel has demonstrated great potential to be a topical wettable dressing for psoriasis treatment.

SUBMITTER: He X

PROVIDER: S-EPMC7471623 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe imiquimod (IMQ)-induced psoriasis mouse model has been used as a model for pathogenic mechanism research, and methotrexate (MTX) is widely employed to treat various clinical manifestations of psoriasis. We explored the underlying pathogenesis of psoriasis and the treatment mechanism of the conventional drugs from the metabolic perspective of the psoriasis mouse model.MethodsMale BALB/c mice were smeared IMQ for 7 days to induce treatment-resistant psoriasis and intragastrically administered 1 mg/kg MTX. We evaluated inflammation of psoriasis-like lesions and therapeutic effects of MTX based on histological changes and immunohistochemistry. Based on gas chromatography-mass spectrometer detection of serum samples, a comprehensive metabolomics analysis was carried out to identify alterations of metabolites.ResultsIt was found that MTX ameliorated psoriatic lesions (representative erythema, scaling, and thickening) by inhibiting proliferation and differentiation of keratinocytes. Using multivariate statistical analysis to process metabolomics data, the results displayed alterations in serum metabolites among mice of the control group, IMQ group, and MTX group. Compared with group, psoriasis mice had the higher level of d-galactose and lower expression of myo-inositol, 9,12-octadecadienoic acid, and cholesterol. In contrast with the model set, serum levels of glycine, pyrrolidone carboxylic acid, d-galactose, and d-mannose were significantly decreased in the MTX group.ConclusionThe differential metabolites, reflecting the perturbation in the pathways of inositol phosphate metabolism; galactose metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and glutathione metabolism, may lead to the pathogenesis of psoriasis, and they are also related to the pharmacological treatment effect of MTX on psoriasis. This study established the foundation for further research on the mechanism and therapeutic targets of psoriasis.

Project description:BackgroundThe polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease of both localized and systemic low-grade inflammation. The Sirtuin1 enzyme thought to mediate the effects of resveratrol is present in skin and resveratrol is known to down regulate NF-κB; an important contributor in the development of psoriasis. Consequently we investigated whether resveratrol has an effect on an Imiquimod induced psoriasis-like skin inflammation in mice and sought to identify candidate genes, pathways and interleukins mediating the effects.MethodsThe study consisted of three treatment groups: A control group, an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was assessed using elements of the Psoriasis Area Severity Index, skin thickness measurements, and histological examination. We performed an RNA microarray from lesional skin and afterwards Ingenuity pathway analysis to identify affected signalling pathways. Our microarray was compared to a previously deposited microarray to determine if gene changes were psoriasis-like, and to a human microarray to determine if findings could be relevant in a human setting.ResultsImiquimod treatment induced a psoriasis-like skin inflammation. Resveratrol significantly diminished the severity of the psoriasis-like skin inflammation. The RNA microarray revealed a psoriasis-like gene expression-profile in the Imiquimod treated group, and highlighted several resveratrol dependent changes in relevant genes, such as increased expression of genes associated with retinoic acid stimulation and reduced expression of genes involved in IL-17 dependent pathways. Quantitative PCR confirmed a resveratrol dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing psoriasis.ConclusionsResveratrol ameliorates psoriasis, and changes expression of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19 mRNA levels in a beneficial manner, which suggests resveratrol, might have a role in the treatment of psoriasis and should be explored further in a human setting.

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Amelioration of imiquimod-induced psoriasis-like dermatitis in mice by DSW therapy inspired hydrogel.

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