Background

Psoriasis is a chronic skin condition associated with interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Recent evidence declares that angiotensin II (Ang II) induces a potent IL-17-related inflammation. Meanwhile, Losartan, an angiotensin one receptor (AT1R) antagonist, attenuates the TH17-related responses. Therefore, we investigated the possible beneficial effects of topically applied Losartan1% ointment on imiquimod (IMQ)-induced psoriasis in mice.

Method

Psoriasis was induced in mice consecutively for five days by topical IMQ on the shaved back. The IMQ-induced psoriasis was treated via topical administration of Losartan1% twice a day. The severity of skin inflammation was evaluated employing Psoriasis Area and Severity Index (PASI) scores. Subsequently, the skin samples were assessed using Baker's scoring system, stereological studies, and biochemical assessment with real-time PCR and immunohistochemistry.

Results

IMQ administration induced plaque-type psoriasis and skin inflammation. We characterized psoriatic lesions by hyperkeratosis, Munro abscess, rete ridges, and marked T-cell infiltrates. IMQ significantly increased epidermal volume, mRNA expression of IL-17a, IL-23, Ang II, AT1R, and TNF-α levels compared with the Placebo group. Topical administration of Losartan1% on IMQ-induced psoriasis significantly reduced the PASI scores and alleviated the erythema and scaling. The treatment significantly decreased the psoriatic thickness and dermal T-cell infiltration. Regarding biochemical assessment, Losartan1% considerably reduced the IMQ-induced increase of IL-17a, Ang II, and AT1R expression in the skin.

Conclusion

Topical Losartan1% significantly alleviates psoriasis by reducing AT1R and IL-17a expression. Our results introduce AT1Rs as a promising therapeutic target in psoriasis and represent a link between angiotensin and TH17-related inflammation. However, the effects of AngII-AT1R systems on IL-17 signaling need to be confirmed by further investigations.

中文翻译：

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氯沙坦软膏减轻咪喹莫特诱导的银屑病样炎症

背景

银屑病是一种与白细胞介素 23/白细胞介素 17 (IL-23/IL-17) 通路相关的慢性皮肤病。最近的证据表明血管紧张素 II (Ang II) 可诱导有效的 IL-17 相关炎症。同时，血管紧张素一受体 (AT1R) 拮抗剂氯沙坦可减弱 TH17 相关反应。因此，我们研究了局部应用氯沙坦 1% 软膏对咪喹莫特 (IMQ) 诱导的小鼠银屑病的可能有益作用。

方法

通过在剃光背部的局部 IMQ 连续五天在小鼠中诱导牛皮癣。IMQ 诱发的银屑病通过每天两次局部施用氯沙坦1% 进行治疗。使用银屑病面积和严重性指数 (PASI) 评分评估皮肤炎症的严重程度。随后，使用贝克评分系统、体视学研究以及实时 PCR 和免疫组织化学的生化评估对皮肤样本进行评估。

结果

IMQ 给药诱导斑块型银屑病和皮肤炎症。我们通过角化过度、Munro 脓肿、网状脊和明显的 T 细胞浸润来表征银屑病病变。与安慰剂组相比，IMQ 显着增加了表皮体积、IL-17a、IL-23、Ang II、AT1R 和 TNF-α 水平的 mRNA 表达。在 IMQ 诱导的银屑病中局部施用氯沙坦 1% 可显着降低 PASI 评分并减轻红斑和鳞屑。该治疗显着降低了银屑病厚度和真皮 T 细胞浸润。关于生化评估，Losartan1% 显着降低了 IMQ 诱导的皮肤中 IL-17a、Ang II 和 AT1R 表达的增加。

结论

外用氯沙坦 1% 通过降低 AT1R 和 IL-17a 表达显着减轻银屑病。我们的研究结果将 AT1Rs 介绍为​​银屑病的有希望的治疗靶点，并代表了血管紧张素和 TH17 相关炎症之间的联系。然而，AngII-AT1R 系统对 IL-17 信号传导的影响需要通过进一步研究来证实。