L. 通过 TLR7/8-MyD88-NF-κB-NLRP3 炎性小体途径改善咪喹莫特诱导的银屑病样皮炎并抑制炎症细胞因子的产生。

L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8-MyD88-NF-κB-NLRP3 Inflammasome Pathway.

机构信息

Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China.

出版信息

Molecules. 2019 Jun 7;24(11):2157. doi: 10.3390/molecules24112157.

DOI:10.3390/molecules24112157

PMID:31181689

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6600670/

Abstract

BACKGROUND

Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. L. is a traditional Chinese medicine that exhibited a significant therapeutic effect on psoriasis in our previous study due to its remarkable anti-inflammatory effect. Meanwhile, the mechanism underlying its effects on psoriasis is still unclear.

METHODS

An imiquimod-induced psoriasis-like dermatitis mouse model was constructed to evaluate the protective effect of the effective part of L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&E) staining, immunohistochemical examination, enzyme-linked immunosorbent assay (ELISA), and Western blot were used to measure the inflammatory cytokines and the protein expression associated with the Toll-like receptor 7- myeloid differentiation primary response gene 88-nuclear Factor-κB-nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8-MyD88-NF-κB-NLRP3) inflammasome pathway.

RESULTS

EPD significantly decreased the PASI, reduced epidermal thickness, and decreased the proliferation and differentiation of epidermal cells in psoriasis-like dermatitis C57BL/6 mice induced by imiquimod (IMQ). Furthermore, EPD reduced the infiltration of CD3+ cells to psoriatic lesions, as well as ameliorated the elevations of intercellular adhesion molecule 1 (ICAM-1) and inhibited the production of imiquimod-induced inflammatory cytokines, including IL-1β, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and interferon-γ (IFN-γ). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKKα, p-IKBα, p-NF-κB, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1β.

CONCLUSION

This study demonstrated that EPD exhibited a protective effect on an imiquimod-induced psoriasis mice model by inhibiting the inflammatory response, which might be ascribed to the inhibition of the TLR7/8-MyD88-NF-κb-NLRP3 inflammasome pathway.

摘要

背景

银屑病是一种慢性、免疫介导的炎症性皮肤病，炎症反应在其发生和发展中起着重要作用。L.是一种中药，在我们之前的研究中，由于其显著的抗炎作用，对银屑病表现出显著的治疗效果。同时，其作用于银屑病的机制尚不清楚。

方法

构建咪喹莫特诱导的银屑病样皮炎小鼠模型，评价 L.有效部位（EPD）的保护作用，通过银屑病面积和严重程度指数（PASI）评分进行验证。采用苏木精和伊红（H&E）染色、免疫组织化学检查、酶联免疫吸附试验（ELISA）和Western blot 检测炎症细胞因子和 Toll 样受体 7-髓样分化初级反应基因 88-核因子-κB-核苷酸结合寡聚化结构域（Nod）样受体家族吡咯烷域包含 3（TLR7/8-MyD88-NF-κB-NLRP3）炎性小体途径相关蛋白的表达。

结果

EPD 显著降低 PASI，减轻表皮厚度，减少咪喹莫特（IMQ）诱导的银屑病样皮炎 C57BL/6 小鼠表皮细胞的增殖和分化。此外，EPD 减少 CD3+细胞浸润到银屑病病灶，并改善细胞间黏附分子 1（ICAM-1）的升高，抑制炎性细胞因子的产生，包括白细胞介素 1β（IL-1β）、白细胞介素 2（IL-2）、白细胞介素 6（IL-6）、白细胞介素 10（IL-10）、白细胞介素 12（IL-12）、白细胞介素 17（IL-17）、白细胞介素 22（IL-22）、白细胞介素 23（IL-23）、肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白 1（MCP-1）和干扰素-γ（IFN-γ）。此外，EPD 降低了 TLR7、TLR8、TRAF6、MyD88、p-IKKα、p-IKBα、p-NF-κB、NLRP3、凋亡相关斑点样蛋白包含半胱天冬氨酸蛋白酶募集域（ASC）、天冬氨酸特异性半胱氨酸蛋白酶 1（caspase-1）和白细胞介素 1β的表达水平。