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Title: Chemokine CXCL16 mediates acinar cell necrosis in cerulein induced acute pancreatitis in mice
Authors: Sakuma, Yojiro
Kodama, Yuzo
Eguchi, Takaaki
Uza, Norimitsu  kyouindb  KAKEN_id
Tsuji, Yoshihisa
Shiokawa, Masahiro  kyouindb  KAKEN_id
Maruno, Takahisa
Kuriyama, Katsutoshi
Nishikawa, Yoshihiro
Yamauchi, Yuki
Tsuda, Motoyuki
Ueda, Tatsuki
Matsumori, Tomoaki
Morita, Toshihiro
Tomono, Teruko
Kakiuchi, Nobuyuki  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-4893-5414 (unconfirmed)
Mima, Atsushi
Sogabe, Yuko
Marui, Saiko
Kuwada, Takeshi
Okada, Akihiko
Watanabe, Tomohiro
Nakase, Hiroshi
Chiba, Tsutomu
Seno, Hiroshi  kyouindb  KAKEN_id
Author's alias: 宇座, 徳光
辻, 喜久
丸野, 貴久
西川, 義浩
津田, 喬之
松森, 友昭
森田, 敏広
渡邉, 智裕
仲瀬 , 裕志
千葉, 勉
妹尾, 浩
Issue Date: 11-Jun-2018
Publisher: Springer Nature
Journal title: Scientific reports
Volume: 8
Thesis number: 8829
Abstract: 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.
Rights: © Te Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/234715
DOI(Published Version): 10.1038/s41598-018-27200-y
PubMed ID: 29891873
Appears in Collections:Journal Articles

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