Department of Dermatology, The First Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Immunodermatology, Ministry of Education Key Laboratory of Immunodermatology, National Joint Engineering Research Center for Diagnosis and Treatment of Immunologic Skin Diseases, The First Hospital of China Medical University, Shenyang, China.
Department of Dermatology, The First Hospital of China Medical University, Shenyang, China; Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Immunodermatology, Ministry of Education Key Laboratory of Immunodermatology, National Joint Engineering Research Center for Diagnosis and Treatment of Immunologic Skin Diseases, The First Hospital of China Medical University, Shenyang, China.
Toxicol Appl Pharmacol. 2022 Sep 15;451:116189. doi: 10.1016/j.taap.2022.116189. Epub 2022 Aug 1.
Toll-like receptor (TLR) 2, along with some chemokines, were found to be overexpressed in rosacea patients. Aryl hydrocarbon Receptor (AhR) activation inhibited the inflammatory responses triggered by TLR activation. The current study was conducted to evaluate the underlying mechanisms of AhR activation in rosacea models.
Seven-week-old female BALB/c mice received twice daily intradermal injections of LL-37 for 2 consecutive days. Thirty minutes after the second LL-37 injection, 1% or 0.5% AhR agonist benvitimod was administrated topically once per day for 3 consecutive days. HaCaT cells were treated with different concentrations of LL-37 and benvitimod, and were further infected with lentivirus to over-express TLR2. Expressions of TLR2, CCL5, CXCL9, CXCL10 and CXCL11 were evaluated using qRT-PCR, Western Blot or ELISA.
AhR activation ameliorated LL-37-induced rosacea-like eruptions in mice by reductions in redness scores, redness areas and dermal inflammatory cell infiltrates. Elevated expressions of TLR2 and chemokines (CCL5, CXCL9, CXCL10 and CXCL11) following LL-37 treatment were decreased by AhR activation. In HaCaT cells receiving LL-37, TLR2 and the four chemokines were up-regulated, and levels of these chemokines were further enhanced after over-expressing TLR2. At 8 h after an administration of 10 μM benvitimod, gene expressions of TLR2 and the four chemokines in LL-37 treated HaCat cells were decreased, while their protein expressions were decreased for 24 h.
AhR activation is beneficial in treating rosacea in a LL-37-induced rosacea mouse model and involves a suppression of the TLR signaling pathway in an HaCaT cell model of rosacea.
Toll 样受体（TLR）2 以及一些趋化因子在酒渣鼻患者中表达过度。芳香烃受体（AhR）的激活抑制了 TLR 激活引发的炎症反应。本研究旨在评估 AhR 激活在酒渣鼻模型中的潜在机制。
7 周龄雌性 BALB/c 小鼠接受两次每日真皮内注射 LL-37，连续 2 天。第二次 LL-37 注射后 30 分钟，每天一次给予 1%或 0.5%AhR 激动剂苯并维莫德局部治疗 3 天。用不同浓度的 LL-37 和苯并维莫德处理 HaCaT 细胞，并进一步用慢病毒感染以过表达 TLR2。使用 qRT-PCR、Western Blot 或 ELISA 评估 TLR2、CCL5、CXCL9、CXCL10 和 CXCL11 的表达。
AhR 激活通过减少红斑评分、红斑面积和真皮炎症细胞浸润，改善了 LL-37 诱导的小鼠酒渣鼻样皮疹。LL-37 处理后 TLR2 和趋化因子（CCL5、CXCL9、CXCL10 和 CXCL11）表达升高，AhR 激活降低了这些趋化因子的表达。在接受 LL-37 处理的 HaCaT 细胞中，TLR2 和四种趋化因子上调，在过表达 TLR2 后，这些趋化因子的水平进一步增强。在给予 10 μM 苯并维莫德 8 小时后，LL-37 处理的 HaCat 细胞中 TLR2 和四种趋化因子的基因表达减少，而其蛋白表达则在 24 小时后减少。
AhR 激活对 LL-37 诱导的酒渣鼻小鼠模型中的酒渣鼻有益，涉及在酒渣鼻 HaCaT 细胞模型中 TLR 信号通路的抑制。
