Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China.
J Eur Acad Dermatol Venereol. 2023 Apr;37(4):796-809. doi: 10.1111/jdv.18725. Epub 2022 Nov 30.
Rosacea is a chronic inflammatory skin disease with increased macrophage infiltration. However, the molecular mechanism remains unclear.
To determine the significance of macrophage infiltration, and the correlation between Guanylate-binding protein 5 (GBP5) and polarization of macrophages in rosacea-like inflammation.
Here we tested the hypothesis that Guanylate-binding protein 5 (GBP5) aggravates rosacea-like skin inflammation by promoting the polarization of the M1 macrophages through the NF-κB signalling pathway. We depleted macrophage by injecting clodronate-containing liposomes. We next explored the association between GBP5 and macrophage in rosacea tissue through transcriptome analysis and immunofluorescence analysis. We evaluated the severity of rosacea-like skin inflammation when BALB/c mice were injected with GBP5 siRNA intradermally daily for three consecutive days. At last, to study the causality of knocking down GBP5-blunted M1 macrophage polarization, THP-1 cell was treated with GBP5 siRNA.
Macrophage depletion ameliorated rosacea-like skin inflammation in mice, implying the important role of macrophages in rosacea. Based on the transcriptome analysis, Guanylate-binding protein 5 (GBP5) was identified as hub gene that was associated with macrophage infiltration in rosacea. Next, we found that GBP5 expression was significantly upregulated in rosacea tissues and positively correlated with macrophage infiltration, the immunofluorescence analysis revealed the co-localization between GBP5 and macrophages. In vivo, silencing of GBP5 attenuated rosacea-like skin inflammation in the LL-37-induced mouse model and suppressed the expression of M1 signature genes such as IL-6, iNOS and TNF-a. In vitro, knocking down GBP5 significantly blunted the polarization of the M1 macrophages partly by repressing the activation of the NF-κB signalling pathways.
Together, our study revealed the important role of macrophages in rosacea and identified GBP5 as a key regulator of rosacea by inducing M1 macrophage polarization via NF-κB signalling pathways.
酒渣鼻是一种慢性炎症性皮肤疾病，其特征为巨噬细胞浸润增加。然而，其分子机制尚不清楚。
确定巨噬细胞浸润的意义，以及在酒渣鼻样炎症中，鸟苷酸结合蛋白 5（GBP5）与巨噬细胞极化之间的相关性。
在这里，我们通过 NF-κB 信号通路，测试了假设，即鸟苷酸结合蛋白 5（GBP5）通过促进 M1 巨噬细胞的极化加重酒渣鼻样皮肤炎症。我们通过注射含有氯膦酸酯的脂质体来耗尽巨噬细胞。接下来，我们通过转录组分析和免疫荧光分析，探索了 GBP5 与酒渣鼻组织中巨噬细胞的关联。我们评估了 BALB/c 小鼠连续 3 天每天皮内注射 GBP5 siRNA 时酒渣鼻样皮肤炎症的严重程度。最后，为了研究敲低 GBP5 减弱 M1 巨噬细胞极化的因果关系，我们用 GBP5 siRNA 处理 THP-1 细胞。
巨噬细胞耗竭可改善小鼠的酒渣鼻样皮肤炎症，表明巨噬细胞在酒渣鼻中起着重要作用。基于转录组分析，我们发现鸟苷酸结合蛋白 5（GBP5）是与酒渣鼻中巨噬细胞浸润相关的关键基因。接下来，我们发现 GBP5 在酒渣鼻组织中的表达显著上调，并与巨噬细胞浸润呈正相关，免疫荧光分析显示 GBP5 与巨噬细胞共定位。在体内，沉默 GBP5 可减轻 LL-37 诱导的小鼠模型中的酒渣鼻样皮肤炎症，并抑制 M1 特征基因如 IL-6、iNOS 和 TNF-a 的表达。在体外，敲低 GBP5 通过抑制 NF-κB 信号通路的激活，显著减弱 M1 巨噬细胞的极化。
总之，我们的研究揭示了巨噬细胞在酒渣鼻中的重要作用，并确定 GBP5 是通过 NF-κB 信号通路诱导 M1 巨噬细胞极化的关键调节因子。
