Silencing of miR-155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation
Silencing of miR-155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation
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DOI：
10.3892/ijmm.2018.3677
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发表时间：
2018-08-01
影响因子：
5.4
通讯作者：
Zhang, Xibao
中科院分区：
文献类型：
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作者：
Luo, Quan;Zeng, Jingxin;Zhang, Xibao
银屑病是一种以鳞屑、红斑、瘙痒为主要临床症状的皮肤病，病程长。此外，它容易复发和难治，极大地影响了患者的身心健康。在本研究中，假设miR-155的功能增加银屑病诱导的炎症，并且其表达可能依赖于炎性小体激活。采用基因芯片和定量聚合酶链反应技术检测miR-155的表达。与正常组织相比，在银屑病的体内模型中miR-155表达水平显著增加，NLR家族pyrin domain containing 3（NLRP 3）的表达也是如此。在体外，使用角质形成细胞诱导的HaCaT细胞作为银屑病模型，证实miR-155的沉默显著降低炎症和NLRP 3/caspase-1信号传导。在体外角质形成细胞模型中，toll样受体4（TLR 4）的激活增强了miR-155诱导的炎症反应。用TLR 4抑制剂或NLRP 3抑制剂治疗逆转了相同细胞系统中miR-155介导的炎症。目前的研究表明，miR-155沉默抑制银屑病相关的炎症反应，通过炎症体NLRP 3的调节。
Psoriasis is a dermatosis with the major clinical symptoms of scale, erythema and itching, and it has a long disease course. In addition, it is easily recurrent and refractory, greatly affecting the physical and mental health of patients. In the present study, it was hypothesized that the function of miR-155 increases psoriasis-induced inflammation and that its expression may be dependent on inflammasome activation. miR-155 expression was examined by gene chip array and quantitative polymerase chain reaction analysis. miR-155 expression levels were significantly increased in an in vivo model of psoriasis compared with normal tissues, as was the expression of NLR family pyrin domain containing 3 (NLRP3). In vitro, using keratinocyte-induced HaCaT cells as a model for psoriasis, silencing of miR-155 was confirmed to significantly decrease inflammation and NLRP3/caspase-1 signaling. Activation of toll-like receptor 4 (TLR4) enhanced the miR-155-induced inflammatory response in the in vitro keratinocyte model. Treatment with a TLR4 inhibitor or an NLRP3 inhibitor reversed the miR-155-mediated inflammation in the same cell system. The present study demonstrated that miR-155 silencing suppressed psoriasis-associated inflammatory responses through inflammasome NLRP3 regulation.