机构:[1]Guangzhou Univ Chinese Med, Guangdong Prov Key Lab Clin Res Tradit Chinese Me, Guangdong Prov Acad Chinese Med Sci, Immunol Sect,Clin Med Coll 2, Guangzhou, Guangdong, Peoples R China; Guangzhou Univ Chinese Med, Guangdong Prov Key Lab Clin Res Tradit Chinese Me, Guangdong Prov Acad Chinese Med Sci, Joint Immunol Program,Clin Med Coll 2, Guangzhou, Guangdong, Peoples R China
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 gamma 8 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 ROR gamma t, IL-17A, IL-6 and TNF alpha. Importantly, it suppressed NF kappa B 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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81803804]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [S2013030011515, 2017A030310124, 2018A030310530]; Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine [YN2016ZDO1, YN2015MS20]; Science and Technology Planning Project of Guangdong Province, China [2017A050506041, 2017B030314166]
第一作者机构:[1]Guangzhou Univ Chinese Med, Guangdong Prov Key Lab Clin Res Tradit Chinese Me, Guangdong Prov Acad Chinese Med Sci, Immunol Sect,Clin Med Coll 2, Guangzhou, Guangdong, Peoples R China; Guangzhou Univ Chinese Med, Guangdong Prov Key Lab Clin Res Tradit Chinese Me, Guangdong Prov Acad Chinese Med Sci, Joint Immunol Program,Clin Med Coll 2, Guangzhou, Guangdong, Peoples R China
通讯作者:
通讯机构:[*1]Guangdong Prov Acad Chinese Med Sci, Immunol Sect, 55 Nei Huan Xi Lu, Guangzhou 510006, Guangdong, Peoples R China[*2]Guangdong Prov Acad Chinese Med Sci, Joint Immunol Program, 55 Nei Huan Xi Lu, Guangzhou 510006, Guangdong, Peoples R China
推荐引用方式(GB/T 7714):
Liu Cuihua,Chen Yuchao,Lu Chuanjian,等.Betulinic acid suppresses Th17 response and ameliorates psoriasis-like murine skin inflammation[J].INTERNATIONAL IMMUNOPHARMACOLOGY.2019,73:343-352.