Betulinic acid suppresses Th17 response and ameliorates psoriasis-like murine skin inflammation
| Autor: | Yuchao Chen, Huazhen Liu, Haiding Huang, Zhenhua Dai, Yong-Yue Xu, Chuanjian Lu, Cuihua Liu, Ling Han, Yuhong Yan, Haiming Chen, Jingwen Deng, Jianan Wei |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_treatment T cell Immunology Anti-Inflammatory Agents Inflammation Pharmacology medicine.disease_cause Autoimmunity Mice RAR-related orphan receptor gamma Psoriasis medicine Immunology and Allergy Animals Betulinic Acid Mice Inbred BALB C business.industry NF-kappa B FOXP3 Nuclear Receptor Subfamily 1 Group F Member 3 medicine.disease Triterpenes Mice Inbred C57BL Cytokine medicine.anatomical_structure Cytokines Th17 Cells Tumor necrosis factor alpha medicine.symptom business Pentacyclic Triterpenes |
| Zdroj: | International immunopharmacology. 73 |
| ISSN: | 1878-1705 |
| Popis: | Psoriasis is a common inflammatory skin disease. Current treatment for psoriasis relies on conventional immunosuppressive agents. However, long-term treatment with global immunosuppression may cause various side effects. Thus, it is compelling to seek alternative drugs for treating psoriasis with potentially less side effects. Betulinic acid (BA) is a naturally occurring pentacyclic triterpene, an ingredient that originally exists in natural plants and lacks systemic toxicity. BA can regulate immunity with anti-fibrotic, anti-inflammatory and antioxidant properties. However, it's unknown whether BA has a therapeutic effect on psoriasis. The objectives of this study were to investigate whether BA attenuates psoriatic skin inflammation and to identify its mechanisms of action. A murine model of imiquimod-induced psoriasis was utilized to evaluate skin lesion while flow cytometry, immunohistochemistry, quantitative RT-PCR and Western blotting analyses were performed for immunoassays. We found that BA treatment alleviated psoriatic symptoms and inflammatory skin lesion. BA lowered the PASI scores, decreased epidermal thickness and reduced T cell infiltration in the skin lesion. Moreover, BA reduced the frequency of IL-17A-expressing CD4+ and γδ T cells in psoriatic mice, but did not alter CD4+FoxP3+ Treg frequency. BA also reduced IL-17A production but increased anti-inflammatory cytokine IL-10 level in serum of the psoriatic mice. Furthermore, BA inhibited gene expression of pro-inflammatory mediators in skin lesions, including RORγt, IL-17A, IL-6 and TNFα. Importantly, it suppressed NFκB signaling in the skin lesion. Finally, BA inhibited T cell proliferation and IL-17A production by CD4+ T-Cells in vitro. Thus, BA attenuates psoriasis and inhibits Th17 development. |
| Databáze: | OpenAIRE |
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