Rosacea is a chronic inflammatory skin disorder characterized by immune response–dependent erythema and pustules. S100A9, a proinflammatory alarmin, has been associated with various inflammation-related diseases. However, the specific role of S100A9 in rosacea remains unexplored. Therefore, our objective was to unravel the role of S100A9 in the pathogenesis of rosacea and its underlying molecular mechanisms. In this study, we show that expression levels of S100A9 were elevated in both the lesions and serum of patients with papulopustular rosacea as well as in lesions of the LL37-induced rosacea-like mouse model. Moreover, the upregulation of S100A9 was correlated with clinical severity and levels of inflammatory cytokines. In addition, we demonstrated that S100A9 promoted the production of proinflammatory factors in HaCaT cells by activating toll-like receptor 4/MyD88/NF-κB signaling pathways. Notably, inhibition of S100A9 suppressed the progression of rosacea-like dermatitis and inflammatory responses in the LL37-induced rosacea-like mouse model through toll-like receptor 4/MyD88/NF-κB signaling pathways. In conclusion, this study illustrated that S100A9 participates in the pathogenesis of rosacea by upregulating toll-like receptor 4/MyD88/NF-κB signaling pathways, thereby promoting rosacea-associated skin inflammation. These results not only expand our understanding of the potential role of S100A9 in the development of rosacea but also offer greater insight toward targeted therapies.

中文翻译：

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S100A9 通过 Toll 样受体 4/MyD88/NF-κB 信号通路加剧红斑痤疮的炎症

红斑痤疮是一种慢性炎症性皮肤病，其特征是免疫反应依赖性红斑和脓疱。 S100A9 是一种促炎警报素，与多种炎症相关疾病有关。然而，S100A9 在红斑痤疮中的具体作用仍有待探索。因此，我们的目标是揭示S100A9在红斑痤疮发病机制中的作用及其潜在的分子机制。在这项研究中，我们发现，在丘疹脓疱性红斑痤疮患者的皮损和血清中，以及在 LL37 诱导的红斑痤疮样小鼠模型的皮损中，S100A9 的表达水平均升高。此外，S100A9 的上调与临床严重程度和炎症细胞因子水平相关。此外，我们证明S100A9通过激活Toll样受体4/MyD88/NF-κB信号通路促进HaCaT细胞中促炎因子的产生。值得注意的是，在 LL37 诱导的酒渣鼻样小鼠模型中，抑制 S100A9 可通过 Toll 样受体 4/MyD88/NF-κB 信号通路抑制酒渣鼻样皮炎和炎症反应的进展。总之，本研究表明S100A9通过上调Toll样受体4/MyD88/NF-κB信号通路参与红斑痤疮的发病机制，从而促进红斑痤疮相关的皮肤炎症。这些结果不仅扩大了我们对 S100A9 在红斑痤疮发展中潜在作用的理解，而且还为靶向治疗提供了更深入的见解。