Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-α/IFN-γ-induced inflammatory response in keratinocytes and T cell-derived IL-17

Lin, Zheng; Ma, Meng; Li, Heng; Qi, Qing; Liu, Yuting; Yan, Yu-xi; Shen, Yunfu; Yang, Xiaoqian; Zhu, Fenghua; He, Shijun; Tang, Wei; Zuo, Jian‐Ping

doi:10.1016/j.phrs.2017.11.012

Cited by 48 publications

(29 citation statements)

References 37 publications

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“…This is accordance with a previous study [24] that investigated the effects of acarbose on IMQ-induced psoriasis-like inflammation of skin of BALB/c mice which exhibited reduced erythema and scaling over the whole period of treatment as well as significant decrease of the epidermal thickness. Also, in agreement with our observations, calcipotriol [8] and betamethasone [28] have been reported to significantly reduce erythema and scaling in IMQ treated mice. Moreover, calcipotriol/betamethasone therapy has been stated to hinder the epidermal thickening in skin biopsy samples of psoriasis patient [56,57] .…”

Section: Discussionsupporting

confidence: 93%

“…It was also described to display as elongated rete ridges with bulbous tips [39] . Rapid keratinocyte proliferation leading to acanthosis [40] has also been explained by continuous release of inflammatory factors from activated T lymphocytes leading to the presence of a sustained set of signals that results in epidermal hyperplasia [8] . Parakeratosis is an epidermal differentiation abnormality, a typical phenomenon for psoriasis skin lesions [26,41] and the underlying cause of scaling of the skin [26] .…”

Section: Discussionmentioning

confidence: 99%

“…The main characters of psoriasis are uncontrolled proliferation of keratinocytes and their abnormal differentiation leading to development of focal erythematous scaly patches which shed constantly. Moreover, a cellular reaction that includes T lymphocytes, dendritic cells (DCs), macrophages and mast cells is involved in psoriasis pathogenesis [7,8] .…”

Section: Introductionmentioning

confidence: 99%

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Comparative Histological Study on the Preventive Role of Acarbose and Calcipotriol/Betamethasone in Mouse Model of Psoriasis-Like Skin Inflammation Induced by Imiquimod

Alghandour

Sabry

Mohsen

2019

Egyptian Journal of Histology

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Introduction: Psoriasis is an autoimmune skin disorder that is symptomized by erythema and scaling. Recently, imiquimod (IMQ) has been used to induce skin inflammation in mice to create a psoriasis model. Aim of the Work: To assess the possible preventive potential of acarbose on psoriasis-like skin inflammation induced by IMQ in adult male mice, and to compare it to calcipotriol/betamethasone applied on the same psoriasis mouse model. Materials and Methods: Thirty four BALB/c mice were classified as the following groups: I(Control), II(IMQ): IMQ-model with topically applied Aldara cream, ІII(Acarbose): IMQ-model treated with Glucobay orally, ІV(Calcipotriol/Betamethasone): IMQ-model treated with Calcipoheal-Cort ointment and V(Acarbose+Calcipotriol/Betamethasone): IMQ-model treated with both Glucobay and Calcipoheal-Cort combined. Haematoxylin & Eosin stain and S100 immunohistochemical staining were performed along with electron microscopic study of skin sections. Mean epidermal thickness and mean number of S100 immuno-positive keratinocytes were measured and measurements were statistically analyzed. Results: Group II mice showed psoriasis-like signs of skin inflammation. Groups III and IV mice showed less signs of inflammation which were markedly attenuated by combination of both of the treatments. Group II demonstrated significant acanthosis and abundant infiltrates of inflammatory cells in the dermis and significantly numerous S100 immuno-positive keratinocytes. Groups III and IV showed significant improvement of these changes which were markedly diminished in group V as it showed almost normal histological structure. Conclusion: Acarbose had an overall beneficial effect on psoriasis-mimicking mouse model triggered by IMQ, almost comparable to that demonstrated by calcipotriol/betamethasone. However, combination of both treatments exerted a more powerful therapeutic effect.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative Histological Study on the Preventive Role of Acarbose and Calcipotriol/Betamethasone in Mouse Model of Psoriasis-Like Skin Inflammation Induced by Imiquimod

Alghandour

Sabry

Mohsen

2019

Egyptian Journal of Histology

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“…1a, c-e). IMQ application induces splenomegaly through systemic inflammatory effects, which is the another characteristic feature of mice model, which might appear due to increased immunological activity and hyperplasia 23,24 . In this context, we found that PPL treatment significantly attenuated the enlarged spleens (Fig.…”

Section: Resultsmentioning

confidence: 99%

Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation

et al. 2020

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Psoriasis is an autoimmune skin disease, where chronic immune responses due to exaggerated cytokine signaling, abnormal differentiation, and evasion of keratinocytes apoptosis plays a crucial role in mediating abnormal keratinocytes hyperproliferation. From the therapeutic perspective, the molecules with strong anti-proliferative and anti-inflammatory properties could have tremendous relevance. In this study, we demonstrated that piperlongumine (PPL) treatment effectively abrogated the hyperproliferation and differentiation of keratinocytes by inducing ROSmediated late apoptosis with loss of mitochondrial membrane potential. Besides, the arrest of cell cycle was found at Sub-G1 phase as a result of DNA fragmentation. Molecularly, inhibition of STAT3 and Akt signaling was observed with a decrease in proliferative markers such as PCNA, ki67, and Cyclin D1 along with anti-apoptotic Bcl-2 protein expression. Keratin 17 is a critical regulator of keratinocyte differentiation, and it was found to be downregulated with PPL significantly. Furthermore, prominent anti-inflammatory effects were observed by inhibition of lipopolysaccharide (LPS)/Imiquimod (IMQ)-induced p65 NF-κB signaling cascade and strongly inhibited the production of cytokine storm involved in psoriasis-like skin inflammation, thus led to the restoration of normal epidermal architecture with reduction of epidermal hyperplasia and splenomegaly. In addition, PPL epigenetically inhibited histone-modifying enzymes, which include histone deacetylases (HDACs) of class I (HDAC1-4) and class II (HDAC6) evaluated by immunoblotting and HDAC enzyme assay kit. In addition, our results show that PPL effectively inhibits the nuclear translocation of p65 and a histone modulator HDAC3, thus sequestered in the cytoplasm of macrophages. Furthermore, PPL effectively enhanced the protein-protein interactions of HDAC3 and p65 with IκBα, which was disrupted by LPS stimulation and were evaluated by Co-IP and molecular modeling. Collectively, our findings indicate that piperlongumine may serve as an anti-proliferative and anti-inflammatory agent and could serve as a potential therapeutic option in treating psoriasis.

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“…The IL-23/IL-17 axis has been reported to be a critical regulator for psoriasis and psoriatic arthritis. Studies have reported that IMQ-induced psoriasis-like skin elicited either protein or mRNA expression of IL-17, IL-23, IL-1β, IL-6, TNF-α, and interferon-γ(INF-γ) in mouse skin [3,[35][36][37] and successful anti-psoriasis treatment inhibited the above-mentioned cytokine expression [35][36][37]. Our study demonstrated a significant increase in IL-23/IL-17 cytokine protein expression after six consecutive days of IMQ application.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid B in Microemulsion Formulation Provided Sufficient Hydration for Dry Skin and Ameliorated the Severity of Imiquimod-induced Psoriasis-like Dermatitis in Mice

et al. 2020

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Psoriasis is a chronic inflammatory skin disorder with a pathogenesis involving the interleukin-23/interleukin-17 axis. Salvianolic acid B exerts several pharmacological effects, such as antioxidation, anti-inflammation, and antitumor effects. The anti-psoriatic effects of salvianolic acid B have not been reported. In this study, we aimed to determine the optimum vehicle for salvianolic acid B, investigate its therapeutic effect on psoriatic-like skin conditions, and explore its underlying mechanisms of action. BALB/c mice were administered topical imiquimod to induce psoriasis-like skin and were then randomly assigned to control, vehicle control, salvianolic acid B in vehicles, and 0.25% desoximetasone ointment treatment groups. Barrier function, cytokine expression, histology assessment, and disease severity were evaluated. The results showed that salvianolic acid B-containing microemulsion alleviated disease severity, reduced acanthosis, and inhibited interleukin-23/interleukin-17 (IL-23/IL-17) cytokines, epidermal proliferation, and increased skin hydration. Our study suggests that salvianolic acid B represents a possible new therapeutic drug for the treatment of psoriasis. In addition, such formulation could obtain high therapeutic efficacy in addition to providing sufficient hydration for dry skin.

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Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-α/IFN-γ-induced inflammatory response in keratinocytes and T cell-derived IL-17

Cited by 48 publications

References 37 publications

Comparative Histological Study on the Preventive Role of Acarbose and Calcipotriol/Betamethasone in Mouse Model of Psoriasis-Like Skin Inflammation Induced by Imiquimod

Comparative Histological Study on the Preventive Role of Acarbose and Calcipotriol/Betamethasone in Mouse Model of Psoriasis-Like Skin Inflammation Induced by Imiquimod

Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation

Salvianolic Acid B in Microemulsion Formulation Provided Sufficient Hydration for Dry Skin and Ameliorated the Severity of Imiquimod-induced Psoriasis-like Dermatitis in Mice

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