Department of Dermatology, China Medical University Hospital, Taichung 404327, Taiwan.
Institute of Nutrition, College of health Care, China Medical University, Taichung 406040, Taiwan.
Biomed Pharmacother. 2023 Oct;166:115307. doi: 10.1016/j.biopha.2023.115307. Epub 2023 Aug 11.
The chronic disease psoriasis is associated with severe inflammation and abnormal keratinocyte propagation in the skin. Tranexamic acid (TXA), a plasmin inhibitor, is used to cure serious bleeding. We investigated whether TXA ointment mitigated Imiquimod (IMQ)-induced psoriasis-like inflammation. Furthermore, this study investigated the effect of noncytotoxic concentrations of TXA on IL-17-induced human keratinocyte (HaCaT) cells to determine the status of proliferative psoriatic keratinocytes. We found that TXA reduced IMQ-induced psoriasis-like erythema, thickness, scaling, and cumulative scores (erythema plus thickness plus scaling) on the back skin of BALB/c mice. Additionally, TXA decreased ear thickness and suppressed hyperkeratosis, hyperplasia, and inflammation of the ear epidermis in IMQ-induced BALB/c mice. Furthermore, TXA inhibited IMQ-induced splenomegaly in BALB/c mouse models. In IL-17-induced HaCaT cells, TXA inhibited ROS production and IL-8 secretion. Interestingly, TXA suppressed the IL-17-induced NFκB signaling pathway via IKK-mediated IκB degradation. TXA inhibited IL-17-induced activation of the NLRP3 inflammasome through caspase-1 and IL1β expression. TXA inhibited IL-17-induced NLRP3 inflammasome activation by enhancing autophagy, as indicated by LC3-II accumulation, p62/SQSTM1 expression, ATG4B inhibition, and Beclin-1/Bcl-2 dysregulation. Notably, TXA suppressed IL-17-induced Nrf2-mediated keratin 17 expression. N-acetylcysteine pretreatment reversed the effects of TXA on NFκB, NLRP3 inflammasomes, and the Nrf2-mediated keratin 17 pathway in IL-17-induced HaCaT cells. Results further confirmed that in the ear skin of IMQ-induced mice, psoriasis biomarkers such as NLRP3, IL1β, Nrf2, and keratin 17 expression were downregulated by TXA treatment. TXA improves IMQ-induced psoriasis-like inflammation in vivo and psoriatic keratinocytes in vitro. Tranexamic acid is a promising future treatment for psoriasis.
慢性疾病银屑病与皮肤中的严重炎症和异常角质形成细胞增殖有关。氨甲环酸（TXA）是一种纤溶酶抑制剂，用于治疗严重出血。我们研究了 TXA 软膏是否减轻了咪喹莫特（IMQ）诱导的银屑病样炎症。此外，本研究还研究了非细胞毒性浓度的 TXA 对 IL-17 诱导的人角质形成细胞（HaCaT）的影响，以确定增殖性银屑病角质形成细胞的状态。我们发现 TXA 减少了 BALB/c 小鼠背部皮肤 IMQ 诱导的银屑病样红斑、厚度、鳞屑和累积评分（红斑加厚度加鳞屑）。此外，TXA 减少了耳厚度，并抑制了 IMQ 诱导的 BALB/c 小鼠耳表皮的过度角化、增生和炎症。此外，TXA 抑制了 BALB/c 小鼠模型中 IMQ 诱导的脾肿大。在 IL-17 诱导的 HaCaT 细胞中，TXA 抑制了 ROS 产生和 IL-8 的分泌。有趣的是，TXA 通过 IKK 介导的 IκB 降解抑制了 IL-17 诱导的 NFκB 信号通路。TXA 通过抑制 caspase-1 和 IL1β 的表达，抑制了 IL-17 诱导的 NLRP3 炎性小体的激活。TXA 通过增强自噬抑制了 IL-17 诱导的 NLRP3 炎性小体的激活，如 LC3-II 积累、p62/SQSTM1 表达、ATG4B 抑制和 Beclin-1/Bcl-2 失调所示。值得注意的是，TXA 抑制了 IL-17 诱导的 Nrf2 介导的角质蛋白 17 的表达。N-乙酰半胱氨酸预处理逆转了 TXA 对 IL-17 诱导的 HaCaT 细胞中 NFκB、NLRP3 炎性小体和 Nrf2 介导的角质蛋白 17 途径的影响。结果进一步证实，在 IMQ 诱导的小鼠耳皮肤中，TXA 处理下调了 NLRP3、IL1β、Nrf2 和角质蛋白 17 的表达等银屑病生物标志物。TXA 改善了体内 IMQ 诱导的银屑病样炎症和体外银屑病角质形成细胞。氨甲环酸是一种有前途的未来银屑病治疗方法。
