Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis

Swindell, William R.; Michaels, Kellie A.; Sutter, Andrew J.; Diaconu, Doina; Fritz, Yi; Xing, Xianying; Sarkar, Mrinal K.; Liang, Yun; Tsoi, Lam C.; Guðjónsson, Jóhann E.; Ward, Nicole L.

doi:10.1186/s13073-017-0415-3

Cited by 118 publications

(114 citation statements)

References 77 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…Mouse back skin was treated with 62.5 mg 5% IMQ or a non-toxic cream once per day for five consecutive days. From the third day the erythema and scaling of IMQ-treated mice were observed which is similar to the reported study [12] (Figure 2(a)). Also the clinical score index is significant higher than control mice (Figure 2(b)).…”

Section: Imq-induced Psoriasis Animal Modelsupporting

confidence: 80%

“…In our study also revealed that the skin barrier protein filaggrin is reduced in the psoriasis patients, although as a long time impaired barrier function was regarded as a vital pathogenesis in atopic dermatitis (AD) [2]. In order to convince these results we use the IMQ-induced psoriasis mouse model [12]. IMQ is a TLR-7/8 agonist and [24].…”

Section: Discussionmentioning

confidence: 99%

“…For the second experiments, a topical dose of 62.5 mg 5% IMQ cream (from the second hospital of Xi'an Jiaotong university) was applied daily to the shaved back region of mice, while a non-toxic lanolin-derived occlusion cream was applied as control (CTL) group. IMQ and CTL treatments were carried out for 5 consecutive days and mice were sacrificed on day 6 by cervical dislocation [12]. Mice were observed everyday mainly on the phenotype and clinical lesions.…”

Section: Animal Preparationmentioning

confidence: 99%

“…Each symptom was graded from 0 to 3 (no symptoms = 0; mild = 1; moderate = 2; and severe = 3). The sum of these individual scores was taken as the overall clinical score [12]. At the end of the day skin biopsy was performed and the infiltrated inflammatory cells were measured using immunofluorescence.…”

Section: Animal Preparationmentioning

confidence: 99%

“…Psoriasis is a common chronic inflammatory skin disease which is characterized by epidermal hyperproliferation and altered differentiation. In Y. Zhang et al Journal of Biosciences and Medicines addition using the imiquimod (IMQ)-induced psoriasis mouse model, which was highly used in reported studies [12], to identify the barrier function is defected in the early phase of psoriasis through down regulated filaggrin expression in vivo. Our results indicate that the defective skin barrier is involved in the development of psoriasis with a reduced expression of filaggrin in human and mice.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Expression of Skin Barrier Protein Filaggrin in Skin Diseases without Atopic Dermatitis

Zhang¹,

Tu²,

Wang³

et al. 2018

JBM

View full text Add to dashboard Cite

The epidermis represents an essential barrier versus a broad range of exogenous stimuli. To form a functional epidermis, keratinocytes express filaggrin which plays a vital role in atopic dermatitis. However the relationship between filaggrin and other skin diseases remains unknown. In our study we chose 5 different common skin diseases and analyzed the expression of filaggrin in the skin using immunohistochemistry. Imiquimod (IMQ)-induced mouse model was used for detecting the filaggrin level and barrier function. The results indicated that the expression of filaggrin is reduced in psoriasis compared to the other skin diseases. Furthermore in vivo study showed that the skin barrier is defected with a decreased expression of filaggrin in IMQ-induced psoriasis mouse model, which is accompanied with an increased level of IL-17/IL-23. In conclusion, the defective skin barrier is involved in the development of psoriasis in human and mice with a reduced expression of filaggrin which may be regulated by the increased level of IL-17/IL-23 in the skin.

show abstract

Section: Imq-induced Psoriasis Animal Modelsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Animal Preparationmentioning

confidence: 99%

Section: Animal Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Expression of Skin Barrier Protein Filaggrin in Skin Diseases without Atopic Dermatitis

Zhang¹,

Tu²,

Wang³

et al. 2018

JBM

View full text Add to dashboard Cite

show abstract

A Localized Aldara (5% Imiquimod)–Induced Psoriasiform Dermatitis Model in Mice Using Finn Chambers

et al. 2020

View full text Add to dashboard Cite

The expanding number of research studies utilizing the imiquimod‐induced psoriasiform dermatitis model attests to the usefulness of this procedure. Advantages of this model include rapid development of the skin response and cost‐effectiveness. A major limitation is that application of imiquimod cream over large areas of skin, as well as licking and ingestion of the cream, may lead to severe systemic inflammation, which can cause a general decline in health, splenomegaly, and death. In this protocol, Finn chambers are used to localize the imiquimod cream to a small area of the skin. This results in production of severe and reproducible psoriatic skin reactions with significantly less imiquimod, greatly reducing the possibility of untoward systemic effects. Moreover, having psoriasiform and control skin areas on the same mice decreases inter‐animal differences. The protocol can be readily adapted for other skin disease models involving topical application of test agents. This article also details functional measurements performed during assays, including skin thickness, blood perfusion, semiquantitative histopathological evaluation, determination of scaling score to monitor psoriatic symptoms, and collection of spleen and body weight data to identify systemic effects. © 2020 The Authors. Basic Protocol: Use of Finn chambers to induce psoriasiform skin reactions with imiquimod Support Protocol 1: Measurement of double‐fold dorsal skin thickness Support Protocol 2: Measurement of blood perfusion Support Protocol 3: Determination of scaling score Support Protocol 4: Semiquantitative histopathological scoring Support Protocol 5: Assessment of systemic side effects in response to imiquimod application

show abstract

Kynureninase contributes to the pathogenesis of psoriasis through pro‐inflammatory effect

Wang

Zhang

et al. 2021

Journal Cellular Physiology

View full text Add to dashboard Cite

Kynureninase (KYNU) is a key enzyme in the tryptophan metabolism pathway with elevated expression in psoriatic lesions relative to normal skin. However, whether KYNU contributes to the pathogenesis of psoriasis remains unknown. We sought to investigate the role of KYNU in psoriasis and its possible regulation mechanism. In the results, KYNU is upregulated in psoriatic skin samples from patients or animal models compared with normal skin control which was assayed in psoriatic patient samples, IMQ‐induced psoriasis‐like skin inflammation in BABL/c mice and M5‐stimulated keratinocyte cell lines by immunohistochemistry (IHC). KYNU knockdown had a trivial impact on keratinocyte proliferation, but significantly inhibited the production of inflammatory cytokines in HaCaT, HEKα, and HEKn cells by quantitative reverse‐transcription polymerase chain reaction, enzyme‐linked immunosorbent assay, and western blot analysis. The 3ʹ‐untranslated region of KYNU contains a conserved target site of a skin‐specific microRNA (miRNA), miR‐203a, as predicted by TargetScan software. Furthermore, miR‐203a exhibited an inversed expression kinetics to KYNU during the development of IMQ‐induced psoriasis‐like skin inflammation in BABL/c mice. Overexpression of miR‐203 subsequently leading to the inhibition of KYNU, could significantly reduce the production of M5‐induced, psoriasis‐related inflammatory factors in keratinocytes. Finally, KYNU inhibitors could alleviate the pathological phenotypes in IMQ‐mice. Our study supported the contributive role of KYNU in the development of psoriasis and provided preliminary evidence for KYNU as a potential therapeutic target in psoriasis.

show abstract

Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis

Cited by 118 publications

References 77 publications

Expression of Skin Barrier Protein Filaggrin in Skin Diseases without Atopic Dermatitis

Expression of Skin Barrier Protein Filaggrin in Skin Diseases without Atopic Dermatitis

A Localized Aldara (5% Imiquimod)–Induced Psoriasiform Dermatitis Model in Mice Using Finn Chambers

Kynureninase contributes to the pathogenesis of psoriasis through pro‐inflammatory effect

Contact Info

Product

Resources

About