title: FTY720 Attenuates Acute Pancreatitis in Hypertriglyceridemic Apolipoprotein CIII Transgenic Mice.
abstract: Hypertriglyceridemic pancreatitis (HTGP) is often encountered clinically as a common form of recurrent acute pancreatitis (AP). It is important to evaluate the management of severe hypertriglyceridemia (HTG) or anti-inflammation in the prophylaxis of HTGP in the clinic. FTY720 (2-amino-2[2-(4-octylphenyl) ethyl]-1, 3-propanediol) is a new anti-inflammatory agent with low toxicity and reported to ameliorate lung injury with pancreatitis in rat. We evaluated its protective affection on AP induced by seven hourly intraperitoneal injection of cerulein in apolipoprotein CIII transgenic mice with severe HTG. FTY720 at 1.5 mg/kg was administered by gastric lavage daily for 3 days before induction of AP. The effects of FTY720 to protect against HTGP were assessed by serum amylase, pancreatic pathological scores, immunostaining, and the expression of inflammatory cytokine genes. As a result, injection of cerulein resulted in more severe pathological changes of AP and higher monocyte chemoattractant protein 1 expression in the pancreas in transgenic than in nontransgenic mice. FTY720 pretreatment improved the pathological severity of AP and decreased the expression of monocyte chemoattractant protein 1 in the pancreas significantly, especially near fourfold reduction in transgenic mice. However, FTY720 did not affect plasma triglyceride levels, and other inflammatory factors and plasma amylase were not correlated with the extent of pancreatic damage in AP with or without FTY720 administration. In summary, our study in a new model, apolipoprotein CIII transgenic mice, demonstrated that HTG mice are susceptible to induction of AP. Prophylactic treatment of FTY720 can significantly attenuate cerulein-induced AP and hence warrant further investigation of sphingosine-1-phosphate receptors agonist for potential clinical application in recurrent attacks of HTGP.
authors.affiliation: *Key Laboratory of Molecular Cardiovascular Science Ministry of Education, Institute of Cardiovascular Science, Peking University; and †Clinical Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Jinjiao
authors.initials: J
authors.lastname: Liu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Abudurexiti
authors.initials: A
authors.lastname: Kayoumu
authors.forename: Yunan
authors.initials: Y
authors.lastname: Wang
authors.forename: Mengyu
authors.initials: M
authors.lastname: Wang
authors.forename: Mingming
authors.initials: M
authors.lastname: Gao
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.forename: George
authors.initials: G
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D053305:Apolipoprotein C-III / Q000235:genetics*; D002108:Ceruletide; D018932:Chemokine CCL2 / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000150:complications*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
chemical_list: D053305:Apolipoprotein C-III; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007166:Immunosuppressive Agents; D002108:Ceruletide; D000681:Amylases; D000068876:Fingolimod Hydrochloride