Chemokine CXCL16 mediates acinar cell necrosis in cerulein induced acute pancreatitis in mice.
Chemokine CXCL16 mediates acinar cell necrosis in cerulein induced acute pancreatitis in mice.
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DOI：
10.1038/s41598-018-27200-y
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发表时间：
2018-06-11
影响因子：
4.6
通讯作者：
Seno H
中科院分区：
文献类型：
--
作者：
Sakuma Y;Kodama Y;Eguchi T;Uza N;Tsuji Y;Shiokawa M;Maruno T;Kuriyama K;Nishikawa Y;Yamauchi Y;Tsuda M;Ueda T;Matsumori T;Morita T;Tomono T;Kakiuchi N;Mima A;Sogabe Y;Marui S;Kuwada T;Okada A;Watanabe T;Nakase H;Chiba T;Seno H
重症急性胰腺炎是一种致死性炎症性疾病，常伴有胰腺坏死。我们的目的是确定一个关键的调节胰腺坏死的发展。使用来自急性胰腺炎（AP）患者的血清的细胞因子/趋化因子阵列显示，血清CXCL 16水平根据胰腺炎的严重程度而升高。在AP的小鼠模型中，随着胰腺坏死的发展，在晚期胰腺腺泡中诱导Cxcl 16表达。Cxcl 16 −/−小鼠对胰腺炎发作的敏感性与野生型（WT）小鼠相似，但更好地抵抗腺泡细胞坏死和中性粒细胞浸润减弱的发展。细胞因子阵列和免疫组织化学显示，Cxcl 16 −/−小鼠胰腺腺泡中Ccl 9（一种中性粒细胞趋化因子）的表达低于WT小鼠。Ccl 9 mRNA的表达诱导胰腺腺泡细胞在体外与Cxcl 16蛋白的刺激，表明Cxcl 16/Ccl 9级联。针对Cxcl 16的中和抗体改善了小鼠AP模型中的胰腺损伤，Ccl 9表达降低，中性粒细胞积聚减少。总之，胰腺腺泡中表达的Cxcl 16通过诱导Ccl 9和随后的中性粒细胞浸润而促进腺泡细胞坏死的发展。CXCL 16可能成为AP治疗的新靶点。
Severe acute pancreatitis is a lethal inflammatory disease frequently accompanied by pancreatic necrosis. We aimed to identify a key regulator in the development of pancreatic necrosis. A cytokine/chemokine array using sera from patients with acute pancreatitis (AP) revealed that serum CXCL16 levels were elevated according to the severity of pancreatitis. In a mouse model of AP, Cxcl16 expression was induced in pancreatic acini in the late phase with the development of pancreatic necrosis. Cxcl16−/− mice revealed similar sensitivity as wild-type (WT) mice to the onset of pancreatitis, but better resisted development of acinar cell necrosis with attenuated neutrophil infiltration. A cytokine array and immunohistochemistry revealed lower expression of Ccl9, a neutrophil chemoattractant, in the pancreatic acini of Cxcl16−/− mice than WT mice. Ccl9 mRNA expression was induced by stimulation with Cxcl16 protein in pancreatic acinar cells in vitro, suggesting a Cxcl16/Ccl9 cascade. Neutralizing antibody against Cxcl16 ameliorated pancreatic injury in the mouse AP model with decreased Ccl9 expression and less neutrophil accumulation. In conclusion, Cxcl16 expressed in pancreatic acini contributes to the development of acinar cell necrosis through the induction of Ccl9 and subsequent neutrophil infiltration. CXCL16 could be a new therapeutic target in AP.
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影响因子：
2.9
作者：
Harris, DM;Flannigan, KL;Wu, SV
通讯作者：
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DOI：
10.1152/ajpgi.00031x.2002
发表时间：
2002-01-01
影响因子：
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通讯作者：
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影响因子：
29.4
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