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A dietary oxysterol, 7-ketocholesterol, exacerbates imiquimod-induced psoriasis-like dermatitis in steatohepatitic mice (Liver)

ABSTRACT: Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease. We previously identified an oxidized derivative of cholesterol, 7-ketocholesterol (7KC), in diet-induced steatohepatitic mice. Here, we investigated whether 7KC exacerbates psoriasis-like dermatitis by accelerating steatohepatitis in mice. A high fat/high cholesterol/high sucrose/bile salt diet (NASH diet) with or without 0.0125% 7KC was fed to C57BL/6 mice (7KC or control group) for three weeks to induce steatohepatitis. 5% imiquimod cream was then applied to the ears and dorsal skin for four days to induce psoriasis-like dermatitis. Hepatic lipid accumulation and inflammatory cell infiltration were exacerbated in the 7KC group compared with the control group after three weeks. Serum tumor necrosis factor-α (TNF-α) levels were also elevated in the 7KC group (108.5±9.8 vs. 83.1±13.1 pg/ml, p<0.005). Imiquimod cream increased the psoriasis area severity index (PASI) score in mice in the 7KC group (9.14±0.75 vs. 5.17±1.17, p<0.0001). Additionally, Tnfa, Il23a, Il17a, and Il22 mRNA levels in the dorsal lesion were significantly upregulated. Finally, Th17 cell differentiation and the TNF signaling pathway were enhanced in the dorsal lesions and liver of mice in the 7KC group. These data suggest that steatohepatitis and psoriasis are linked by a potent, diet-related factor.

ORGANISM(S): Mus musculus

PROVIDER: GSE214836 | GEO | 2022/12/27

REPOSITORIES: GEO

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A dietary oxysterol, 7-ketocholesterol, exacerbates imiquimod-induced psoriasis-like dermatitis in steatohepatitic mice (Dorsal skin)

Project description:Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease. We previously identified an oxidized derivative of cholesterol, 7-ketocholesterol (7KC), in diet-induced steatohepatitic mice. Here, we investigated whether 7KC exacerbates psoriasis-like dermatitis by accelerating steatohepatitis in mice. A high fat/high cholesterol/high sucrose/bile salt diet (NASH diet) with or without 0.0125% 7KC was fed to C57BL/6 mice (7KC or control group) for three weeks to induce steatohepatitis. 5% imiquimod cream was then applied to the ears and dorsal skin for four days to induce psoriasis-like dermatitis. Hepatic lipid accumulation and inflammatory cell infiltration were exacerbated in the 7KC group compared with the control group after three weeks. Serum tumor necrosis factor-α (TNF-α) levels were also elevated in the 7KC group (108.5±9.8 vs. 83.1±13.1 pg/ml, p<0.005). Imiquimod cream increased the psoriasis area severity index (PASI) score in mice in the 7KC group (9.14±0.75 vs. 5.17±1.17, p<0.0001). Additionally, Tnfa, Il23a, Il17a, and Il22 mRNA levels in the dorsal lesion were significantly upregulated. Finally, Th17 cell differentiation and the TNF signaling pathway were enhanced in the dorsal lesions and liver of mice in the 7KC group. These data suggest that steatohepatitis and psoriasis are linked by a potent, diet-related factor.

2022-12-27 | GSE214835 | GEO

Expression data from Imiquimod-induced psoriasis mouse model

Project description:Psoriasis is a chronic inflammatory skin disorder that is predominantly characterized by sharply demarcated chronic erythematous plaques. Although its etiological mechanisms are largely unknown, recent evidence suggests that the topical application of imiquimod (IMQ) cream causes psoriasis-like skin inflammation in humans and mice. Skin examined 4 hours after IMQ cream treatment. Results provide insight into the role of each knockout mice phenotype in the response to IMQ-induced psoriasis model.

2017-10-06 | GSE104603 | GEO

Expression data from IMQ-induced psoriasis-like skin inflammation in miR-146a-/- and C57BL6J mice

Project description:miR-146a acts as a negative feedback regulator of inflammation. To investigate the role of miR-146a in psoriasis psoriasiform skin inflammation was indeuced in Mir-146a-/- and wild type mice (C57BL6J) by topical applciation of imiquimod (IMQ)-cream (Aldara). Gene expression profiling (Affymetrix) was used to identify transcriptomic changes associated with psoriasis-like skin inflammation in wild type vs. miR-146a -/-mice. A daily topical dose of 31.25 mg of Aldara cream (5% IMQ) was applied on the right ear of miR-146a -/- and C57BL/6 mice on three consecutive days to induce psorisis-like skin inflammation. Mice were sacrificed at day 4. Ear flaps were collected for total RNA extraction and hybridization on Affymatrix GeneTitan plate format Gene ST 2.1 (mouse).

2016-02-19 | E-GEOD-78057 | biostudies-arrayexpress

Epigenetic silencing of SFRP4 contributes to epidermal hyperplasia in psoriasis

Project description:To investigate the gene expression of imiquimod induced psoriasis-like mouse model, we have employed whole genome microarray as a discovery platform to identify genes differentially expressed compared with wild type C57BL6 mouse exposed to the vehicle of imiquimod. C57BL/6J mice at 6 to 8 weeks of age were applied to a daily topical dose of 62.5 mg of IMQ cream (5%) on the shaved back for 7 consecutive days. Control mice were treated with a same dose of vehicle cream.The total RNA was extracted by using TRIzol.

2014-08-28 | E-GEOD-60804 | biostudies-arrayexpress

Expression data from IMQ-induced psoriasis-like skin inflammation in miR-146a-/- and C57BL6J mice

2016-02-19 | GSE78057 | GEO

Comparison of Genes in Imiquimod-treated and Control Tumors

Project description:The goal of the study is to examine changes in tumor gene expression after imiquimod treatment. RNA was extracted from spontaneous tumors in control mice (n=4) and in imiquimod-treated mice (n=4). Gene expression was compared between the control group and the treated group. In the imiquimod treatment group, the mice received topical treatment of 5% imiquimod cream (Aldara) on shaved skin at the site of spontaneous tumors for one treatment cycle (3 consecutive days). RNA was extracted from 4 spontaneous tumors from neu-tg mice treated with topical imiquimod for 1 cycle and 4 spontaneous tumors from control mice

2010-06-24 | E-GEOD-20032 | biostudies-arrayexpress

Comparison of Genes in Imiquimod-treated and Control Tumors

2010-01-26 | GSE20032 | GEO

Expression data from anisomycin- and imiquimod-induced dermatitis

Project description:We provide a new psoriasis mouse model which is induced by p38 activation in skin. We compared the individual transcriptomic proﬁles of anisomycin and imiquimod-induced dermatitis. We used microarrays to compare the gene expression pattern between anisomycin- and imiquimod- induced dermatitis.

2019-02-15 | GSE110658 | GEO

Soluble adenylyl cyclase induces type 17 inflammation and is a potential therapeutic target in psoriasis

Project description:Cyclic AMP (cAMP) has a key role in psoriasis pathogenesis, as indicated by the therapeutic efficacy of phosphodiesterase inhibitors that prevent the degradation of cAMP. However, whether soluble adenylate cyclase (sAC) (encoded by the ADCY10 gene), which is an important source for cAMP, is involved in Th17 cell-mediated inflammation or could be an alternative therapeutic target in psoriasis is unknown. We have utilized the imiquimod model of murine psoriasiform dermatitis to address this question. Adcy10-/- mice had reduced erythema, scaling and swelling in the skin and Th17 cell numbers in the draining lymph nodes, compared with wild-type mice after induction of psoriasiform dermatitis with imiquimod. During Th17 polarization in vitro, naïve T cells from Adcy10-/- mice were unable to differentiate to Th17 cells and RNA-seq analysis revealed that sAC was also essential for Th17 cell activation. Interestingly, sAC did not impact Th17 lineage-defining transcription factors (such as RORc and cMAF) but rather was required for CREB-dependent gene expression. Finally, topical application of small molecule sAC inhibitors (sACi) reduced imiquimod-induced psoriasiform dermatitis and IL17 gene expression in the skin. Collectively, these findings demonstrate that sAC is a key factor for inducing type 17 inflammation in the skin and sACi could provide an alternative class of topical therapeutics for psoriasis.

2021-10-01 | GSE175470 | GEO

Expression data from mouse abdominal skin

Project description:Psoriasis-like skin inflammation was indused by 5 daily topical applications of imiquimod (IMQ), a TLR7/8 agonist, or vehicle, in mice fed a high fat diet (HFD) or control chow diet (CD). Skin samples were collected at day 6.

2019-06-30 | GSE68750 | GEO

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