Tu Ying, Yang Zhenghui, He Yunting, Wang Tingyu, Hua Piyan, Yao Qiuyan, Gu Hua
Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People's Republic of China.
Arch Dermatol Res. 2025 Apr 1;317(1):658. doi: 10.1007/s00403-025-04060-x.
To explore the role of macrophage polarization induced by circadian rhythm disorder (CRD) in the aggravated inflammatory response of rosacea. The rosacesis-like animal model was established by intradermal injection of Cathelicidin antimicrobial peptide LL-37 (LL37) into the back of mice. HE staining, Western blot and immunofluorescence detection were used to investigate the effect of circadian rhythm disorder on the expression of inflammatory factors and macrophage polarization in rosacea. Overexpression of Brain and Muscle ARNT-Like 1 (Oe-Bmal1) was transfected into HaCaT cells and M0 macrophages treated with LL37 in vitro to investigate the role of Muscle ARNT-Like 1 (Bmal1) on rosacea. In LL37-induced rosacea mice, circadian rhythm disruption (CRD) suppressed the expression of circadian clock proteins, including Bmal1, Circadian Locomotor Output Cycles Kaput (Clock), Period Circadian Protein 1 (Per1), Period Circadian Protein 2 (Per2), Nuclear Receptor Subfamily 1 Group D Member 1 (Rev-erbα), and Retinoic Acid Receptor-Related Orphan Receptor Alpha (RORα), and induced the polarization of macrophages in rosacea-like mice towards the M1 phenotype. Subsequently, the expression of inflammatory factors, including Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Interleukin-1 beta (IL-1β), was promoted, which aggravated the inflammatory response of skin lesions. Over-expression of Bmal1 significantly increased the expression level of clock proteins and inhibited the polarization of macrophages to M1 type, consequently inhibiting the expression of inflammatory factors in the cell model of rosacea. Circadian rhythm disorder may aggravate the inflammatory response of rosacea by affecting macrophage polarization, which indicates that paying attention to regular sleep and rest may be necessary for the treatment and management of rosacea.
探讨昼夜节律紊乱（CRD）诱导的巨噬细胞极化在酒渣鼻炎症反应加重中的作用。通过向小鼠背部皮内注射抗菌肽LL-37（LL37）建立酒渣鼻样动物模型。采用苏木精-伊红（HE）染色、蛋白质免疫印迹法（Western blot）和免疫荧光检测法，研究昼夜节律紊乱对酒渣鼻炎症因子表达和巨噬细胞极化的影响。将脑和肌肉芳香烃受体核转运蛋白样蛋白1（Bmal1）过表达载体转染至体外经LL37处理的人永生化角质形成细胞（HaCaT细胞）和M0巨噬细胞中，以研究Bmal1在酒渣鼻发病中的作用。在LL37诱导的酒渣鼻小鼠中，昼夜节律紊乱（CRD）抑制了包括Bmal1、昼夜运动输出周期蛋白（Clock）、周期蛋白1（Per1）、周期蛋白2（Per2）、核受体亚家族1 D组成员1（Rev-erbα）和视黄酸受体相关孤儿受体α（RORα）在内的生物钟蛋白的表达，并诱导酒渣鼻样小鼠中的巨噬细胞向M1表型极化。随后，肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）等炎症因子的表达被促进，加重了皮肤损伤的炎症反应。Bmal1过表达显著增加了生物钟蛋白的表达水平，并抑制巨噬细胞向M1型极化，从而抑制了酒渣鼻细胞模型中炎症因子的表达。昼夜节律紊乱可能通过影响巨噬细胞极化加重酒渣鼻的炎症反应，这表明注意规律作息可能对酒渣鼻的治疗和管理很有必要。
