The effect of Fractalkine in the progression of chronic pancreatitis

慢性胰腺炎是一种不可逆的胰腺炎性疾病，以慢性炎症细胞浸润、腺泡细胞变性和纤维化发展为特征，导致胰腺外分泌和内分泌功能受损。最近，已经在几种初始炎性疾病中证明了fractalkine/CX 3CR 1介导的炎症的作用。因此，我们首先阐明了慢性胰腺炎患者血清Fractalkine水平的升高，尤其是在早期。接下来，使用DBTC慢性胰腺炎模型大鼠，我们鉴定胰腺星状细胞为Fractalkine表达的主要来源。在体外研究中，我们证实了胰腺星状细胞中病原体相关分子模式（如LPS）诱导的Fractalkine分泌增加。有趣的是，PMA和乙醇，这是蛋白激酶C的底物，可以协同诱导Fractalkine释放。此外，我们通过抑制试验阐明了参与Fractalkine释放的多个应激激酶和金属蛋白酶。提示Fractalkine在慢性胰腺炎的发生发展中起重要作用。

Chronic pancreatitis, an irreversible inflammatory disease of the pancreas, is characterized by chronic inflammatory cell infiltration, acinar cell degeneration, and development of fibrosis, which lead to impairment of pancreatic exocrine and endocrine function. Recently, a role for fractalkine/CX3CR1-mediated inflammation has been demonstrated in several initial inflammatory disorders. Therefore, at first, we elucidated the elevation of serum Fractalkine level in patients with chronic pancreatitis, especially in early-stage. Next, using DBTC chronic pancreatitis model rats, we identified pancreatic stellate cells as a main source of Fractalkine expression. In vitro study, we confirmed the increased secretion of Fractalkine induced by pathogen-associated molecular patterns, such as LPS, in pancreatic stellate cells. Interestingly, both PMA and ethanol, which were substrates for protein kinase C, could synergistically induce Fractalkine release. Furthermore, we elucidated multiple stress kinase and metalloprotease involving in Fractalkine release by inhibitory assays. In conclusion, it is suggested that Fractalkine plays an important factor in progression of chronic pancreatitis.