Strain specific response of mice to IMQ-induced psoriasis

Abstract

Objectives Psoriasis is an autoimmune, inflammatory disease that needs a reliable animal model. Imiquimod (IMQ)-induced psoriasis is a widely used preclinical tool for psoriasis research. However, this model is sensitive to the genetic variation of mice. The present study explores mice’s genetic background on disease stability and severity induced by IMQ. Methods Three distinct strains of mice (Balb/c, C57BL/6, and Swiss albino) were divided into four groups (Vaseline, IMQ, IMQ+Clobetasol, and IMQ+Curcumin). Psoriasis area severity index (PASI) score, ear/back skin thickness, body weight alterations, and histopathological examination were employed to analyze disease severity. The spleen index studied the systemic effect. Strain effect on oxidative stress induced by IMQ was evaluated by estimating antioxidant factors, superoxide dismutase (SOD), catalase, and glutathione (GSH). Results IMQ application resulted in increased PASI score, thickness, and alterations in body weight, confirming disease development in all the mice. However, the disease stability/severity between these strains was not identical. Although IMQ application caused splenomegaly, IMQ+curcumin treated C57BL/6 mice demonstrated a synergistic effect of IMQ and curcumin on the spleen resulting in increased splenomegaly. Decreased cellular enzyme activity in SOD, Catalase, and levels of GSH was observed in IMQ challenged mice, indicating the participation of the redox system in the genesis of the disease that was comparable among the strains. Conclusions These results indicate the existence of strain-dependent development of the disease. The Swiss model was found to be better in terms of disease severity and stability than other models. Further, a detailed mechanistic study might help to explain the pathological difference between these strains.

Efficacy and safety of curcumin in psoriasis: preclinical and clinical evidence and possible mechanisms

“…Among the preclinical studies, eight were in vivo studies ( Jain et al, 2016 ; Jia and Fang, 2017 ; Mao et al, 2017 ; Sun et al, 2017 ; Qu, 2018 ; Zhang et al, 2019 ; Jin et al, 2020 ; Badanthadka et al, 2021 ), and the treatment of imiquimod (IMQ)-induced psoriasis-like mice comprised oral ( Jia and Fang, 2017 ; Qu, 2018 ) and topical ( Jain et al, 2016 ; Mao et al, 2017 ; Sun et al, 2017 ; Zhang et al, 2019 ; Jin et al, 2020 ; Badanthadka et al, 2021 ) CUR. Four studies ( Jain et al, 2016 ; Jia and Fang, 2017 ; Mao et al, 2017 ; Qu, 2018 ) used BALB/c mice, and four studies ( Sun et al, 2017 ; Zhang et al, 2019 ; Jin et al, 2020 ; Badanthadka et al, 2021 ) used C57BL mice. Two studies ( Jia and Fang, 2017 ; Qu, 2018 ) reported intervention with CUR gavage, and six studies ( Jain et al, 2016 ; Mao et al, 2017 ; Sun et al, 2017 ; Zhang et al, 2019 ; Jin et al, 2020 ; Badanthadka et al, 2021 ) used a topical intervention method.…”

“…Four studies ( Jain et al, 2016 ; Jia and Fang, 2017 ; Mao et al, 2017 ; Qu, 2018 ) used BALB/c mice, and four studies ( Sun et al, 2017 ; Zhang et al, 2019 ; Jin et al, 2020 ; Badanthadka et al, 2021 ) used C57BL mice. Two studies ( Jia and Fang, 2017 ; Qu, 2018 ) reported intervention with CUR gavage, and six studies ( Jain et al, 2016 ; Mao et al, 2017 ; Sun et al, 2017 ; Zhang et al, 2019 ; Jin et al, 2020 ; Badanthadka et al, 2021 ) used a topical intervention method. Topical CUR has been formulated into different dosage forms with improved penetration and efficacy, including tacrolimus and CUR co-loading ( Jain et al, 2016 ), CUR-loaded nanoparticles ( Sun et al, 2017 ), CUR-loaded nanoparticles incorporated in silk fibroin hydrogel ( Mao et al, 2017 ), and CUR-loaded hyaluronic acid-modified ethosomes ( Zhang et al, 2019 ).…”

“…Five studies ( Jia and Fang, 2017 ; Sun et al, 2017 ; Zhang et al, 2019 ; Jin et al, 2020 ; Badanthadka et al, 2021 ) assessed the total scores in CUR-treated psoriasis model mice on day 6, and a meta-analysis showed that CUR significantly reduced the total scores compared to controls (std.MD: −6.50%; 95% CI: −10.10 to −2.90; p = 0.0004). Six studies ( Jain et al, 2016 ; Mao et al, 2017 ; Sun et al, 2017 ; Zhang et al, 2019 ; Jin et al, 2020 ; Badanthadka et al, 2021 ) assessed the scores for erythema and scaling on day 6, and four studies ( Jain et al, 2016 ; Mao et al, 2017 ; Jin et al, 2020 ; Badanthadka et al, 2021 ) assessed the scores for lesion thickness. A meta-analysis showed that CUR significantly improved erythema (std.MD: −2.88%; 95% CI: −4.57 to −1.19; p = 0.0008), scaling (std.MD: −3.19%; 95% CI: −5.17 to −1.21; p = 0.002), and lesion thickness (std.MD: 2.42−; 95% CI: 3.30 to −1.53; p < 0.00001) in psoriatic-like mice compared to controls.…”

“…A meta-analysis of four studies ( Jain et al, 2016 ; Sun et al, 2017 ; Zhang et al, 2019 ; Badanthadka et al, 2021 ) in Table 4 showed that psoriasis-like mice had significantly reduced ear thickness after 6 days of CUR treatment compared to controls (std.MD: 1.80%; 95% CI: −3.20 to −0.41; p = 0.01).…”

Tumor-derived PD-L1 + exosomes with natural inflammation tropism for psoriasis-targeted treatment

“…The mice were randomly assigned to three treatment groups, i.e., the control, IMQ, and therapy groups. To establish the IMQ-induced psoriasis-like model, mice were treated with a daily topical dose of 62.5 mg of IMQ-cream (5%; Mingxinlidi, Sichuan, China) on the back for seven consecutive days based on a previous study [47]. The negative control was treated with the same dose of Vaseline cream alone.…”