PSORI-CM02 formula alleviates imiquimod-induced psoriasis via affecting macrophage infiltration and polarization
PSORI-CM02 formula alleviates imiquimod-induced psoriasis via affecting macrophage infiltration and polarization
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DOI：
10.1016/j.lfs.2019.117231
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发表时间：
2020-02-15
期刊：
影响因子：
6.1
通讯作者：
Han, Ling
中科院分区：
文献类型：
--
作者：
Li, Leng;Zhang, Hong-yu;Han, Ling
银屑病是一种以巨噬细胞浸润真皮层为特征的难治性皮肤病。巨噬细胞可以同时分化为两种不同的功能亚型，M1和M2，这一过程受到微环境、细胞因子和JAK/STAT通路的影响。PSORI-CM 02是一种用于缓解银屑病症状并调节T细胞分化和上皮细胞增殖的新型中药。然而，PSORI-CM 02对咪喹莫特（imiquimod，IMQ）诱导的银屑病及真皮内巨噬细胞浸润和极化的影响尚不清楚。主要方法：采用咪喹莫特诱导的银屑病小鼠模型和小鼠腹腔巨噬细胞株RAW264.7体外M1/M2极化模型，观察PSORI-CM 02对皮肤的治疗作用及其分子机制。PSORI-CM 02能显著改善咪喹莫特所致小鼠皮肤损伤，减少巨噬细胞浸润。经PSORI-CM 02方治疗后，小鼠M1巨噬细胞介质显著减少，而M2介质显著增加。类似地，在体外，在LPS和IL-4存在的情况下，PSORI-CM 02分别抑制M1巨噬细胞增殖，并增加M2巨噬细胞增殖。在PSORI-CM 02处理的细胞中，LPS诱导的TNF-α、iNOS和IL-1 β的表达升高降低，而IL-4诱导的Arg-1、Fizz-1、Ym-1和IL-10的表达升高。最后，我们发现PSORI-CM 02在巨噬细胞极化中的作用与调节STAT 1和STAT 6的表达有关，STAT 1和STAT 6分别被LPS和IL-4.Significance激活：我们的新发现表明，PSORI-CM 02可能通过调节真皮层巨噬细胞的浸润和极化来治疗银屑病。
Aims: Psoriasis is a refractory skin disease characterized by macrophage cell infiltrated in the dermal layer. Macrophages can simultaneously polarize into two distinct functional subtypes, M1 and M2, and this process is affected by the microenvironment, cytokines and JAK/STAT pathways. Formula PSORI-CM02 is a novel Chinese medicine used to alleviate psoriasis symptoms and regulate T cell differentiation and epithelial cell proliferation. However, the effects of PSORI-CM02 in imiquimod (IMQ)-induced psoriasis and macrophage infiltration and polarization in the dermis remain unknown.Main methods: Imiquimod induced psoriasis mice model and M1/M2 polarization model on mice peritoneal macrophages cell line RAW264.7 in vitro were used to observe the therapeutic effect of PSORI-CM02 on skin and its molecular mechanisms.Key findings: PSORI-CM02 can significantly improve skin lesions and reduce macrophage infiltration in mice induced by imiquimod. After treatment with PSORI-CM02 formula, M1 macrophage mediators were significantly reduced, while M2 mediators were significantly increased in mice. Similarly in vitro, M1 macrophage proliferation was suppressed and M2 macrophage proliferation was elevated by PSORI-CM02 in the presence of LPS and IL-4, respectively. The elevated expression of TNF-alpha, iNOS, and IL-1 beta induced by LPS was reduced, while the expression of Arg-1, Fizz-1, Ym-1, and IL-10 induced by IL-4 was elevated in PSORI-CM02-treated cells. Finally, we found that the effects of PSORI-CM02 in macrophage polarization were associated with regulation of STAT1 and STAT6 expression, which were activated by LPS and IL-4, respectively.Significance: Our novel findings reveal that PSORI-CM02 may possess therapeutic action in psoriasis treatment by regulating the infiltration and polarization of macrophages in the dermal layer.