Shou Chenfeng, Sun Yuansong, Zhang Qiao, Zhang Wenqiang, Yan Qi, Xu Tao, Li He
Department of Emergency Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Research Center of Minimally Invasive Intervention, Anhui Medical University, Hefei, 230032, China.
Inflammation. 2024 Dec 18. doi: 10.1007/s10753-024-02194-0.
Acute pancreatitis (AP) is a common acute inflammatory abdominal condition. Severe acute pancreatitis (SAP) can provoke a systemic inflammatory response and lead to multiple organ failure. The S100A9 protein, recognized as a major inflammatory biomarker, plays a significant role in both infection and inflammatory responses. Despite its known role in inflammation, the precise role of S100A9 in AP remains poorly understood. This study aimed to elucidate the potential role of S100A9 in AP and investigate the underlying mechanism. We employed a mouse model of AP and the AR42J cell line to investigate the functional role of S100A9. The effect of S100A9 on pancreatic injury and the expression of inflammatory factors (IL-6, IL-1β, and TNF-α) was assessed through targeted inhibition of S100A9 expression in the mouse model of AP. Furthermore, the modulatory effect of cerulein-induced inflammatory responses on AR42J cells was assessed after adding the S100A9 recombinant protein. In the mouse model of AP, targeted inhibition of S100A9 markedly ameliorated pancreatic injury and significantly decreased the expression levels of IL-6, IL-1β, and TNF-α. Moreover, increased levels of S100A9 were positively correlated with elevated expression of receptor for advanced glycation endproducts (RAGE) in pancreatic acinar cells. In AR42J cells, the introduction of S100A9 recombinant protein enhanced RAGE expression and exacerbated cerulein-induced inflammatory response. S100A9 inhibition significantly alleviated the pancreatic inflammatory response by downregulating RAGE expression, thereby improving AP.
急性胰腺炎（AP）是一种常见的急性炎症性腹部疾病。重症急性胰腺炎（SAP）可引发全身炎症反应并导致多器官功能衰竭。S100A9蛋白被认为是一种主要的炎症生物标志物，在感染和炎症反应中均发挥重要作用。尽管已知其在炎症中的作用，但S100A9在AP中的具体作用仍知之甚少。本研究旨在阐明S100A9在AP中的潜在作用并探究其潜在机制。我们采用AP小鼠模型和AR42J细胞系来研究S100A9的功能作用。通过在AP小鼠模型中靶向抑制S100A9的表达，评估S100A9对胰腺损伤和炎症因子（IL-6、IL-1β和TNF-α）表达的影响。此外，在添加S100A9重组蛋白后，评估雨蛙肽诱导的AR42J细胞炎症反应的调节作用。在AP小鼠模型中，靶向抑制S100A9可显著改善胰腺损伤，并显著降低IL-6、IL-1β和TNF-α的表达水平。此外，S100A9水平的升高与胰腺腺泡细胞中晚期糖基化终产物受体（RAGE）表达的升高呈正相关。在AR42J细胞中，引入S100A9重组蛋白可增强RAGE表达并加剧雨蛙肽诱导的炎症反应。抑制S100A9可通过下调RAGE表达显著减轻胰腺炎症反应，从而改善AP。
